替米沙坦对慢性间断性缺氧小鼠血压及心肌血管紧张素转化酶、血管紧张素转化酶2的影响
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摘要
目的通过探索睡眠呼吸暂停综合征(sleep apnea syndrome, SAS)引起的慢性间断性缺氧(chronic intermittent hypoxia, CIH)对肾素-血管紧张素系统(renin angiotensin system, RAS)影响及血管紧张素受体阻滞剂(Angiotensin Receptors Blocker, ARB)的保护作用,探讨SAS对心血管系统损害的可能机制。
方法将32只健康雄性C57B6J小鼠随机分为CIH组、ARB替米沙坦干预组、空气模拟对照组和空白对照组,进行12周的模型试验。免疫组织化学方法检测实验小鼠心肌细胞血管紧张素转化酶(angiotensin converting enzyme, ACE)、血管紧张素转化酶2(angiotensin converting enzyme 2, ACE2)、血管紧张素II(angiotensin II, AngII)表达情况,并检测小鼠血压的情况。
结果(1)小鼠收缩压:CIH组小鼠收缩压明显升高,ARB干预后则收缩压下降:CIH组小鼠(113.8125±11.59414mmHg)与空气模拟对照组(99.6875±8.31065mmHg)(P=0.004)、空白对照组(104.6875±5.713 mmHg)(P=0.049)、ARB干预组(78.625±8.90325 mmHg)(P=0.000)差别均有统计学意义。ARB干预组与空白对照组(P=0.000)、空气模拟对照组(P=0.000)、CIH组(P=0.000)差别均有统计学意义。而空白对照组与空气模拟对照组间(P=0.27),差别无统计学意义。(2)小鼠舒张压:ARB干预组舒张压较其他组下降。ARB干预组(52.5±10.78359 mmHg)与空白对照组(71.1875±7.17604 mmHg)(P=0.000)、空气模拟对照组(66.5625±6.64636 mmHg)(P=0.003)、CIH组(71.1875±9.14931 mmHg)(P=0.000)差别均有统计学意义。而空白对照组与空气模拟对照组(P=0.291)、空白对照组与CIH组(P=1.000)、空气模拟对照组与CIH组(P=0.291),差别无统计学意义。(3)心脏ACE免疫组化:CIH组心脏ACE明显升高,ARB干预后有所下降,但与CIH相比差别无统计学意义。CIH组小鼠(0.034900±0.0129777)与空气模拟对照组(0.005238±0.0025928)(P=0.000)、空白对照组(0.004738±0.0025618)(P=0.000),ARB干预组小鼠(0.025100±0.0061184)与空气模拟对照组(P=0.000)、空白对照组(P=0.000)差别均有统计学意义。而CIH组与ARB干预组(P=0.161)差别无统计学意义,空气模拟对照组与空白对照组(P=0.798)差别无统计学意义。(4)心脏ACE2免疫组化:ARB干预组ACE2最高,CIH组次之。CIH组小鼠(0.052200±0.0191767)与空气模拟对照组(0.029313±0.0135514)(P=0.008)、空白对照组(0.017488±0.0131051)(P=0.000)、ARB干预组(0.072850±0.0175356)(P=0.016),ARB干预组小鼠与空气模拟对照组(P=0.000)、空白对照组(P=0.000)、CIH组(P=0.016)差别均有统计学意义。而空气模拟对照组与空白对照组(P=0.152)差别无统计学意义。(5)心脏AngII免疫组化:ARB干预组AngII最高,CIH组次之。ARB干预组(0.149025±0.0216644)与CIH组(0.095922±0.0328323)(P=0.004)、空气模拟对照组(0.020684±0.0107095)(P=0.000)、空白对照组(0.015019±0.0069788) (P=0.000),CIH组小鼠与ARB干预组(P=0.004)、空气模拟对照组(P=0.000)、空白对照组(P=0.000)差别均有统计学意义。而空气模拟对照组与空白对照组(P=0.248)差别无统计学意义。
结论:(1)慢性间断性缺氧可引起收缩压升高,心脏局部ACE2、ACE、AngII的表达升高。
(2)使用ARB干预后,可使心脏局部ACE2、AngII升高更为明显,血压下降。
Objective To observe the effect of chronic intermittent hypoxia in sleep apnea syndrome patients on renin angiotensin system and the protection of angiotensin receptors blocker on cardiovascular system, so as to explore the mechanism which sleep apnea syndrome act on cardiovascular system.
Methods 32 healthy male C57B6Jmice were randomly divided into 4 groups: the CIH group, the telmisartan treatment group,the air control group, and the blank control group,and 8 mice in each group.The period of chronic intermittent hypoxia last for 12weeks. Angiotensin converting enzyme(ACE)、angiotensin converting enzyme2 (ACE2) and angiotensin II(AngII)in the mice cardiac myocyte were tested by immunohistochemistry. The blood pressure were measured as well.
Results (1)For comparsion of levels of systolic blood pressure,it was significantly higher in the CIH group than other groups and came down after ARB treatment. It was significantly different between the CIH group(113.8125±11.59414mmHg)and the air control group(99.6875±8.31065mmHg)(P=0.004)、the CIH group and the blank control group(104.6875±5.713 mmHg)(P=0.049)、the CIH group and the ARB treatment group(78.625±8.90325 mmHg)(P=0.000)、the ARB treatment group and the blank control group(P=0.000)、the ARB treatment group and the air control group(P=0.000)、the ARB treatment group and the CIH group(P=0.000).There was no differences between the air control group and the blank control group . (2)For comparsion of levels of diastolic blood pressure,it was significantly lower than other groups after ARB treatment. It was significantly different between the ARB treatment group(52.5±10.78359 mmHg)the blank control group(71.1875±7.17604 mmHg)(P=0.000)、the ARB treatment group and the air control group(66.5625±6.64636 mmHg)(P=0.003)、the ARB treatment group and the CIH group(71.1875± 9.14931mmHg)(P=0.000). There was no differences between the air control group and the blank control group(P=0.291)、the blank control group and the CIH group(P=1.000)、the air control group and and the CIH group(P=0.291). (3)For comparsion of levels of ACE immunohistochemisty in mice’hearts,it was significantly higher in the CIH group than other groups and came down after ARB treatment.. It was significantly different between the CIH group(0.034900±0.0129777)and the air control group(0.005238±0.0025928)(P=0.000)、the CIH group and the blank control group(0.004738±0.0025618)(P=0.000),the ARB treatment group(0.025100±0.0061184)and the air control group(P=0.000)、the ARB treatment group and the blank control group(P=0.000).But there was no significant differences between the CIH group and the ARB treatment group(P=0.161)、the air control group and the blank control group(P=0.798). (4)For comparsion of levels of ACE2 immunohistochemisty in mice’hearts,it was highest in the ARB treatment group,followed by the CIH group . It was significantly different between the CIH group(0.052200±0.0191767)and the air control group(0.029313±0.0135514)(P=0.008)、the CIH group and the blank control group(0.017488±0.0131051)(P=0.000)、the CIH group and the ARB treatment group(0.072850±0.0175356)(P=0.016)、the ARB treatment group and the air control group(P=0.000)、the ARB treatment group and the blank control group、the ARB treatment group and the CIH group(P=0.016). There was no significant differences between the air control group and the blank control group(P=0.152). (5)For comparsion of levels of AngII immunohistochemisty in mice’hearts,it was highest in the ARB treatment group,followed by the CIH group. It was significantly different between the ARB treatment group (0.149025±0.0216644)and the CIH group(0.095922±0.0328323)(P=0.004)、the ARB treatment group and the air control group(0.020684±0.0107095)(P=0.000)、the ARB treatment group and the blank control group(0.015019±0.0069788) (P=0.000),the CIH group and the ARB treatment group(P=0.004)、the CIH group and the air control group(P=0.000)、the CIH group and the blank control group(P=0.000). There was no significant differences between the air control group and the blank control group(P=0.248).
Conclusion(1)This experiment confirmed that chronic intermittent hypoxia might induce high systolic blood pressure and the expression of ACE、ACE2 and AngII in mice hearts.
(2)After ARB treatment, the expression of ACE2 and AngII in mice hearts got higher and the blood pressure came down.
方法将32只健康雄性C57B6J小鼠随机分为CIH组、ARB替米沙坦干预组、空气模拟对照组和空白对照组,进行12周的模型试验。免疫组织化学方法检测实验小鼠心肌细胞血管紧张素转化酶(angiotensin converting enzyme, ACE)、血管紧张素转化酶2(angiotensin converting enzyme 2, ACE2)、血管紧张素II(angiotensin II, AngII)表达情况,并检测小鼠血压的情况。
结果(1)小鼠收缩压:CIH组小鼠收缩压明显升高,ARB干预后则收缩压下降:CIH组小鼠(113.8125±11.59414mmHg)与空气模拟对照组(99.6875±8.31065mmHg)(P=0.004)、空白对照组(104.6875±5.713 mmHg)(P=0.049)、ARB干预组(78.625±8.90325 mmHg)(P=0.000)差别均有统计学意义。ARB干预组与空白对照组(P=0.000)、空气模拟对照组(P=0.000)、CIH组(P=0.000)差别均有统计学意义。而空白对照组与空气模拟对照组间(P=0.27),差别无统计学意义。(2)小鼠舒张压:ARB干预组舒张压较其他组下降。ARB干预组(52.5±10.78359 mmHg)与空白对照组(71.1875±7.17604 mmHg)(P=0.000)、空气模拟对照组(66.5625±6.64636 mmHg)(P=0.003)、CIH组(71.1875±9.14931 mmHg)(P=0.000)差别均有统计学意义。而空白对照组与空气模拟对照组(P=0.291)、空白对照组与CIH组(P=1.000)、空气模拟对照组与CIH组(P=0.291),差别无统计学意义。(3)心脏ACE免疫组化:CIH组心脏ACE明显升高,ARB干预后有所下降,但与CIH相比差别无统计学意义。CIH组小鼠(0.034900±0.0129777)与空气模拟对照组(0.005238±0.0025928)(P=0.000)、空白对照组(0.004738±0.0025618)(P=0.000),ARB干预组小鼠(0.025100±0.0061184)与空气模拟对照组(P=0.000)、空白对照组(P=0.000)差别均有统计学意义。而CIH组与ARB干预组(P=0.161)差别无统计学意义,空气模拟对照组与空白对照组(P=0.798)差别无统计学意义。(4)心脏ACE2免疫组化:ARB干预组ACE2最高,CIH组次之。CIH组小鼠(0.052200±0.0191767)与空气模拟对照组(0.029313±0.0135514)(P=0.008)、空白对照组(0.017488±0.0131051)(P=0.000)、ARB干预组(0.072850±0.0175356)(P=0.016),ARB干预组小鼠与空气模拟对照组(P=0.000)、空白对照组(P=0.000)、CIH组(P=0.016)差别均有统计学意义。而空气模拟对照组与空白对照组(P=0.152)差别无统计学意义。(5)心脏AngII免疫组化:ARB干预组AngII最高,CIH组次之。ARB干预组(0.149025±0.0216644)与CIH组(0.095922±0.0328323)(P=0.004)、空气模拟对照组(0.020684±0.0107095)(P=0.000)、空白对照组(0.015019±0.0069788) (P=0.000),CIH组小鼠与ARB干预组(P=0.004)、空气模拟对照组(P=0.000)、空白对照组(P=0.000)差别均有统计学意义。而空气模拟对照组与空白对照组(P=0.248)差别无统计学意义。
结论:(1)慢性间断性缺氧可引起收缩压升高,心脏局部ACE2、ACE、AngII的表达升高。
(2)使用ARB干预后,可使心脏局部ACE2、AngII升高更为明显,血压下降。
Objective To observe the effect of chronic intermittent hypoxia in sleep apnea syndrome patients on renin angiotensin system and the protection of angiotensin receptors blocker on cardiovascular system, so as to explore the mechanism which sleep apnea syndrome act on cardiovascular system.
Methods 32 healthy male C57B6Jmice were randomly divided into 4 groups: the CIH group, the telmisartan treatment group,the air control group, and the blank control group,and 8 mice in each group.The period of chronic intermittent hypoxia last for 12weeks. Angiotensin converting enzyme(ACE)、angiotensin converting enzyme2 (ACE2) and angiotensin II(AngII)in the mice cardiac myocyte were tested by immunohistochemistry. The blood pressure were measured as well.
Results (1)For comparsion of levels of systolic blood pressure,it was significantly higher in the CIH group than other groups and came down after ARB treatment. It was significantly different between the CIH group(113.8125±11.59414mmHg)and the air control group(99.6875±8.31065mmHg)(P=0.004)、the CIH group and the blank control group(104.6875±5.713 mmHg)(P=0.049)、the CIH group and the ARB treatment group(78.625±8.90325 mmHg)(P=0.000)、the ARB treatment group and the blank control group(P=0.000)、the ARB treatment group and the air control group(P=0.000)、the ARB treatment group and the CIH group(P=0.000).There was no differences between the air control group and the blank control group . (2)For comparsion of levels of diastolic blood pressure,it was significantly lower than other groups after ARB treatment. It was significantly different between the ARB treatment group(52.5±10.78359 mmHg)the blank control group(71.1875±7.17604 mmHg)(P=0.000)、the ARB treatment group and the air control group(66.5625±6.64636 mmHg)(P=0.003)、the ARB treatment group and the CIH group(71.1875± 9.14931mmHg)(P=0.000). There was no differences between the air control group and the blank control group(P=0.291)、the blank control group and the CIH group(P=1.000)、the air control group and and the CIH group(P=0.291). (3)For comparsion of levels of ACE immunohistochemisty in mice’hearts,it was significantly higher in the CIH group than other groups and came down after ARB treatment.. It was significantly different between the CIH group(0.034900±0.0129777)and the air control group(0.005238±0.0025928)(P=0.000)、the CIH group and the blank control group(0.004738±0.0025618)(P=0.000),the ARB treatment group(0.025100±0.0061184)and the air control group(P=0.000)、the ARB treatment group and the blank control group(P=0.000).But there was no significant differences between the CIH group and the ARB treatment group(P=0.161)、the air control group and the blank control group(P=0.798). (4)For comparsion of levels of ACE2 immunohistochemisty in mice’hearts,it was highest in the ARB treatment group,followed by the CIH group . It was significantly different between the CIH group(0.052200±0.0191767)and the air control group(0.029313±0.0135514)(P=0.008)、the CIH group and the blank control group(0.017488±0.0131051)(P=0.000)、the CIH group and the ARB treatment group(0.072850±0.0175356)(P=0.016)、the ARB treatment group and the air control group(P=0.000)、the ARB treatment group and the blank control group、the ARB treatment group and the CIH group(P=0.016). There was no significant differences between the air control group and the blank control group(P=0.152). (5)For comparsion of levels of AngII immunohistochemisty in mice’hearts,it was highest in the ARB treatment group,followed by the CIH group. It was significantly different between the ARB treatment group (0.149025±0.0216644)and the CIH group(0.095922±0.0328323)(P=0.004)、the ARB treatment group and the air control group(0.020684±0.0107095)(P=0.000)、the ARB treatment group and the blank control group(0.015019±0.0069788) (P=0.000),the CIH group and the ARB treatment group(P=0.004)、the CIH group and the air control group(P=0.000)、the CIH group and the blank control group(P=0.000). There was no significant differences between the air control group and the blank control group(P=0.248).
Conclusion(1)This experiment confirmed that chronic intermittent hypoxia might induce high systolic blood pressure and the expression of ACE、ACE2 and AngII in mice hearts.
(2)After ARB treatment, the expression of ACE2 and AngII in mice hearts got higher and the blood pressure came down.
引文
1.Rey S, Valdés G, Iturriaga R. Pathophysiology of obstructive sleep apnea-associated hypertension. Rev Med Chil. 2007 Oct;135(10):1333-1342.
2. Van Kats JP, Danser AH, van Meegen J, Verdouw PD, and Schalekamp MA. Angiotensin production by the heart: a quantitative study in pigs with the use of radiolabeled angiotensin infusions. Circulation 98: 73–81.
3. Nagai N, Oike Y, Noda K, Urano T, Kubota Y, Ozawa Y, Shinoda H, Koto T, Shinoda K, Inoue M, Tsubota K, Yamashiro K, Suda T, Ishida S. Suppression of ocular inflammation in endotoxin-induced uveitis by blocking the angiotensin II type 1 receptor. Invest Ophthalmol Vis Sci. 2005 Aug;46(8):2925-2931.
4. Glen E. Foster, Marc J. Poulin , Patrick J. Hanly. Intermittent hypoxia and vascular function: implications for obstructive sleep apnoea. Experimental Physiology 92(1); 51-65.
5. Tasali E, Ip MS. Obstructive sleep apnea and metabolic syndrome: alterations in glucose metabolism and inflammation. Proc Am Thorac Soc. 2008 Feb 15;5(2):207-217.
6. Fletcher EC, Lesske J, Qian W, et al. Episodic hypoxia causes diurnal elevation of systemic blood pressure in rats. Hypertension, 1992, 19:555-561.
7.陈晓阳,曾奕明,黄子扬,陶耕,郑兴中,李永加.慢性间断缺氧小鼠缺氧诱导因子1α的研究.中华结核和呼吸杂志.2005;28(2):93-96.
8.宋爱玲,曾奕明,陈晓阳.慢性缺氧/再氧合小鼠模型实验研究.国际呼吸杂志.2006;26(6):408-411.
9. Yuan ZM, Chen BY, Wang PX, Li SY, Chen YL, Dong LX. Changes of angiotensin II and its receptor during the development of chronic intermittent hypoxia-induced hypertension in rats. Zhonghua Jie He He Hu Xi Za Zhi. 2004 Sep;27(9):577-580.
10.Carey RM, Siragy HM. Newly recognized components of the renin-angiotensin system: potential role in cardiovascular and renal regulation. Endocr Rev. 2005; 24: 261–271.
11. Pagliaro P, Penn C. Rethinking the rennin-Angiotensisn system and its role in cardiovascular regulation. Cardiovasc Drugs Ther. 2005; 19: 77–87.
12. Yamada HF, Fabris B, Allen AM, Jackson B, Johnston CI, Mendelsohn AO.Localization of angiotensin converting enzyme in rat heart. Circ Res. 1991; 68: 141–149.
13. Martin Paul, Ali Poyan Mehr and Reinhold Kreutz. Physiology of Local Renin-Angiotensin Systems. Physiol. Rev. 2006;86: 747-803.
14.De Mello WC, Cherry RC, Manivannann S. Electrophysiologic and morphologic abnormalities in the failing heart: effect of enalapril on the electrical properties. J Card Fail. 1997; 3: 53–61.
15. De Mello WC. Cell coupling and impulse propagation in the failing heart. J Cardiovasc Electrophysiol. 1999; 10: 1409–1420.
16. De Mello WC, Crespo MJ. Correlation between changes in morphology, electrical properties, and angiotensin-converting enzyme activity in the failing heart. Eur J Pharmacol. 1999; 378: 187–194.
17.Lam SY, Fung ML, Leung PS.Regulation of the angiotensin -converting enzyme activity by a time-course hypoxia in the carotid body. J Appl Physiol 2004,96: 809-813.
18. Morrell NW, Danilov SM, Satyan KB, Morris KG, Stenmark KR.Right ventricular angiotensin converting enzyme activity and expression is increased during hypoxic pulmonary hypertension. Cardiovasc Res. 1997 May;34(2):393-403.
19. Morrell NW, Atochina EN, Morris KG, Danilov SM, Stenmark KR.Angiotensin converting enzyme expression is increased in small pulmonary arteries of rats with hypoxia-induced pulmonary hypertension. J Clin Invest. 1995 Oct;96(4):1823-1833.
20. Kay JM, Keane PM, Suyama KL, Gauthier D.Lung angiotensin converting enzyme activity in chronically hypoxic rats. Thorax. 1985 Aug;40(8):587-591.
21.Davidson D, Stalcup SA, Mellins RB. Angiotensin-converting enzyme activity and its modulation by oxygen tension in the guinea pig fetal-placental unit. Circ Res. 1981 Feb;48(2):286-291.
22. Vijay Koka,Xiao Ru Huang,Arthur C.K. Chung,WanshengWang,Luan D. Truong, and Hui Yao Lan. Angiotensin II Up-Regulates Angiotensin I Converting Enzyme (ACE), but Down-Regulates ACE2 via the AT1-ERK/p38 MAP Kinase Pathway. The American Journal of Pathology, 2008 May;172(5): 1174–1183.
23.钟毅,李家富. ANG(1- 7)与高血压保护作用.中国心血管病研究2008;6(9):702-706.
24. Tipnis SR, Hooper NM, Hyde R, Karran E, Christie G, and Turner AJ. A human homolog of angiotensin-converting enzyme. Cloning and functional expression as a captopril-insensitive carboxypeptidase. J Biol Chem. 2000; 275: 33238–33243
25. Donoghue M, Hsieh F, Baronas E, Godbout K, Gosselin M, Stagliano N, Donovan M, Woolf B, Robison K, Jeyaseelan R, Breitbart RE, Acton, SA novel angiotensin-converting enzyme-related carboxypeptidase (ACE2) converts angiotensin I to angiotensin 1–9. Circ Res. 2002; 87: E1–E9.
26.Donoghue M, Hsieh F, Baronas E, et al. A novel angiotensin-converting enzyme-related carboxypeptidase (ACE2) converts angiotensin I to angiotensin 1-9. Circ. Res. 2000;87:E1–E9.
27.Burrell LM, Risvanis J, Kubota E, et al. Myocardial infarction increases ACE2 expression in rat and humans. Eur. Heart J. 2005;26:369–375.
28. Harmer D, Gilbert M, Borman R, Clark KL. Quantitative mRNA expression profiling of ACE 2, a novel homologue of angiotensin converting enzyme. FEBS Lett. 2002; 532: 107–110
29. Komatsu T, Suzuki Y, Imai J, Sugano S, Hida M, Tanigami A, Muroi S, Yamada Y, Hanaoka KK. Molecular cloning, mRNA expression and chromosomal localization of mouse angiotensin-converting enzyme-related carboxypeptidase (mACE2). DNA Seq. 2002; 13: 217–220.
30.Yamamoto K, Ohishi M, Katsuya T, et al. Deletion of Angiotensin-Converting Enzyme 2 Accelerates Pressure Overload-Induced Cardiac Dysfunction by Increasing Local Angiotensin II. Hypertension. 2006;47:718–726.
31.Zisman LS, Keller RS, Weaver B, Lin Q, Speth R, Bristow MR, Canver CC. Increased angiotensin-(1–7)-forming activity in failing human heart ventricles. Evidence for upregulation of the angiotensin-converting enzyme homologue ACE2. Circulation. 2003; 108: 1707.
32. Goulter A, Goddard MJ, Allen JC, Clark KL. ACE2 gene expression is up-regulated in the human failing heart. BMC Med. 2004; 2: 19.
33.Johnston CI Tissue angiotensin converting enzyme in cardiac and vascular hypertrophy, repair, and remodeling. Hypertension. 1994; 23: 258–2680.
34. Ferrario CM, Trask AJ, Jessup JA. Advances in the biochemical and functional roles of angiotensin converting enzyme 2 and angiotensin-(1–7) in the regulation of cardiovascular function. Am J Physiol Heart Circ Physiol. 2005; 289: H2281–H2290.
35. De Mello WC, Cherry RC, Manivannann S. Electrophysiologic and morphologic abnormalities in the failing heart: effect of enalapril on the electrical properties. J Card Fail. 1997; 3: 53–61.
36.Ocaranza MP, Godoy I, Jalil JE, et al. Enalapril Attenuates Downregulation of Angiotensin-Converting Enzyme 2 in the Late Phase of Ventricular Dysfunction in Myocardial Infarcted Rat. Hypertension. 2006;48:572–578.
37. Burchill L, Velkoska E, Dean RG, Lew RA, Smith AI, Levidiotis V, Burrell LM. Acute kidney injury in the rat causes cardiac remodelling and increases angiotensin-converting enzyme 2 expression. Exp. Physiol. 2008;93:622–630.
38.Zhang R, Wu Y, Zhao M, Liu C, Zhou L, Shen S, Liao S, Yang K, Li Q, Wan H. Role of HIF-1alpha in the regulation ACE and ACE2 expression in hypoxic human pulmonary artery smooth muscle cells. Am J Physiol Lung Cell Mol Physiol. 2009 Oct;297(4):631-640.
39.K. KRAMKOWSKI, A. MOGIELNICKI, W. BUCZKO. THE PHYSIOLOGICAL SIGNIFICANCE OF THE ALTERNATIVE PATHWAYS OF ANGIOTENSIN II PRODUCTION. JOURNAL OF PHYSIOLOGY AND PHARMACOLOGY 2006, 57(4): 529-539.
40. Michiya IGASE, Katsuhiko KOHARA, Tokihisa NAGAI, Tetsuro MIKI, Carlos M. FERRARIO. Increased Expression of Angiotensin Converting Enzyme 2 in Conjunction with Reduction of Neointima by Angiotensin II Type 1 Receptor Blockade. Hypertens Res. 2008 Mar;31(3):553-559.
41. Gray MO, Long CS, Kalinyak JE, Li HT, and Karliner JS. Angiotensin II stimulates cardiac myocyte hypertrophy via paracrine release of TGF-beta 1 and endothelin-1 from fibroblasts. Cardiovasc Res 1998(40): 352–363.
42. Hirsch AT, Talsness CE, Schunkert H, Paul M, and Dzau VJ. Tissue-specific activation of cardiac angiotensin converting enzyme in experimental heart failure. Circ Res 1991(69): 475–482.
43.Cigola E, Kajstura J, Li B, Meggs LG, and Anversa P. Angiotensin II activates programmed myocyte cell death in vitro. Exp Cell Res1997 ;231: 363–371.
44. Ferrario CM, Trask AJ, Jessup JA. Advances in biochemical and functional roles of angiotensin-converting enzyme 2 and angiotensin-(1-7) in regulation of cardiovascular function. Am J Physiol. 2005;289:2281–2290.
45.Ferrario CM, Jessup J, Chappell MC, et al. Effect of angiotensin-converting enzyme inhibition and angiotensin II receptor blockers on cardiac angiotensin-converting enzyme 2. Circulation. 2005;111:2605–2610.
46.Joergen O, Dendorfer A, Dominiak P. Cardiovascular and renal function of angiotensin II type-2 receptor. Cardiovascular Res. 2004; 62: 460–467.
47.Rey S, Valdés G, Iturriaga R. Pathophysiology of obstructive sleep apnea-associated hypertension. Rev Med Chil. Epub 2007 Dec 20;135(10):1333-1342.
48. Yuan ZM, Chen BY, Wang PX, Li SY, Chen YL, Dong LX. Changes of angiotensin II and its receptor during the development of chronic intermittent hypoxia-induced hypertension in rats. Zhonghua Jie He He Hu Xi Za Zhi. 2004 Sep;27(9):577-580.
49. Lai CJ, Yang CC, Hsu YY, Lin YN, Kuo TB. Enhanced sympathetic outflow and decreased baroreflex sensitivity are associated with intermittent hypoxia-induced systemic hypertension in conscious rats.J Appl Physiol. 2006 Jun;100(6):1974-1982.
1. Alvarez-Sala Walther JL. Obstructive sleep apnea syndrome.An R Acad Nac Med (Madr). 2002;119(1):197-211.
2. Glen E. Foster, Marc J. Poulin , Patrick J. Hanly. Intermittent hypoxia and vascular function: implications for obstructive sleep apnoea. Experimental Physiology 92(1):51-65.
3. Tasali E, Ip MS. Obstructive sleep apnea and metabolic syndrome: alterations in glucose metabolism and inflammation. Proc Am Thorac Soc. 2008 Feb 15;5(2):207-217.
4. Rey S, Valdés G, Iturriaga R. Pathophysiology of obstructive sleep apnea-associated hypertension. Rev Med Chil. Epub 2007 Dec 20;135(10):1333-1342.
5. Yuan ZM, Chen BY, Wang PX, Li SY, Chen YL, Dong LX. Changes of angiotensin II and its receptor during the development of chronic intermittent hypoxia-induced hypertension in rats. Zhonghua Jie He He Hu Xi Za Zhi. 2004 Sep;27(9):577-580.
6. Eugene C. Fletcher. Physiological and Genomic Consequences of Intermittent Hypoxia Invited Review: Physiological consequences of intermittent hypoxia: systemic blood pressure. J Appl Physiol 2001(90): 1600-1605.
7. Lai CJ, Yang CC, Hsu YY, Lin YN, Kuo TB. Enhanced sympathetic outflow and decreased baroreflex sensitivity are associated with intermittent hypoxia-induced systemic hypertension in conscious rats.J Appl Physiol. 2006 Jun;100(6):1974-1982.
8. Prabhakar NR. Oxygen sensing during intermittent hypoxia: cellular and molecular mechanisms. J Appl Physiol. 2001 May;90(5):1986-1994.
9.陈晓阳,曾奕明,黄子扬,陶耕,郑兴中,李永加.慢性间断缺氧小鼠缺氧诱导因子1α的研究.中华结核和呼吸杂志.2005;28(2):93-96.
10. Jurkovicova I, Celec P, Mucska I, Hodosy J. On the origin of cardiovascular complications of sleep apnea syndrome by the means of molecular interactions. Bratisl Lek Listy. 2003;104(4-5):167-173.
11. Chen L, Einbinder E, Zhang Q, Hasday J, Balke CW, Scharf SM. Oxidative stress and left ventricular function with chronic intermittent hypoxia in rats.Am J Respir Crit Care Med. 2005 Oct 1;172(7):915-20.
12. Chao J, Wood JG, Gonzalez NC. Alveolar hypoxia, alveolar macrophages, and systemic inflammation. Respir Res. 2009 (22);10-54.
13. Sun J, Sukhova GK, Yang M, Wolters PJ, MacFarlane LA, Libby P, Sun C, Zhang Y, Liu J, Ennis TL, Knispel R, Xiong W, Thompson RW, Baxter BT, Shi GP. Mast cells modulate the pathogenesis of elastase-induced abdominal aortic aneurysms in mice. J Clin Invest. 2007 Nov;117(11):3359-3368.
14. Neri Serneri GG, Boddi M, Modesti PA, Coppo M, Cecioni I, Toscano T, Papa ML, Bandinelli M, Lisi GF, Chiavarelli M. Cardiac angiotensin II participates in coronary microvessel inflammation of unstable angina and strengthens the immunomediated component. Circ Res. 2004 25;94(12):1630-1637.
15. Wolf G. Free radical production and angiotensin. Curr Hypertens Rep. 2002; 2: 167–173.
16. Morgan BJ. Vascular consequences of intermittent hypoxia. Adv Exp Med Biol. 2007;618:69-84.
17.Van Kats JP, Danser AH, van Meegen J, Verdouw PD, and Schalekamp MA. Angiotensin production by the heart: a quantitative study in pigs with the use of radiolabeled angiotensin infusions. Circulation 1998(98): 73–81.
18.王云英,王培林. ACE及其基因多态性与心脏间质病.国外医学遗传学分册2004; 27(1): 27-30.
19. Carey RM, Siragy HM. Newly recognized components of the renin-angiotensin system: potential role in cardiovascular and renal regulation. Endocr Rev. 2005; 24: 261–271.
20. Pagliaro P, Penn C. Rethinking the rennin-Angiotensisn system and its role in cardiovascular regulation. Cardiovasc Drugs Ther. 2005; 19: 77–87.
21.Yamada HF, Fabris B, Allen AM, Jackson B, Johnston CI, Mendelsohn AO. Localization of angiotensin converting enzyme in rat heart. Circ Res. 1991; 68: 141–149.
22. Martin Paul, Ali Poyan Mehr and Reinhold Kreutz. Physiology of Local Renin-Angiotensin Systems. Physiol. Rev. 86: 747-803.
23. Deddish PA, Marcic B, Jackman HL, Wang HZ, Skidgel RA, Erdos EG. N-domain-specific substrate and C-domain inhibitors of angiotensin-converting enzyme: angiotensin-(1–7) and keto-ACE. Hypertension. 1998; 31: 912–917.
24.钟毅,李家富. ANG(1- 7)与高血压保护作用.中国心血管病研究2008;6(9):702-706.
25. Inagami T. The renin angiotensin system. Essays Biochem. 1994; 28: 147–164.
26.K. KRAMKOWSKI, A. MOGIELNICKI, W. BUCZKO. THE PHYSIOLOGICAL SIGNIFICANCE OF THE ALTERNATIVE PATHWAYS OF ANGIOTENSIN II PRODUCTION. JOURNAL OF PHYSIOLOGY AND PHARMACOLOGY 2006, 57(4): 529-539.
27.Michiya IGASE, Katsuhiko KOHARA, Tokihisa NAGAI, Tetsuro MIKI, Carlos M. FERRARIO. Increased Expression of Angiotensin Converting Enzyme 2 in Conjunction with Reduction of Neointima by Angiotensin II Type 1 Receptor Blockade. Hypertens Res. 2008 Mar;31(3):553-559.
28.Joergen O, Dendorfer A, Dominiak P. Cardiovascular and renal function of angiotensin II type-2 receptor. Cardiovascular Res. 2004; 62: 460–467.
29.Levy BI. Can angiotensin II type 2 receptors have deleterious effects in cardiovascular disease? Implications for therapeutic blockade of the renin-angiotensin system. Circulation. 2004;109:8–13.
30. Tipnis SR, Hooper NM, Hyde R, Karran E, Christie G, and Turner AJ. A human homolog of angiotensin-converting enzyme. Cloning and functional expression as a captopril-insensitive carboxypeptidase. J Biol Chem. 2000; 275: 33238–33243
31. Donoghue M, Hsieh F, Baronas E, Godbout K, Gosselin M, Stagliano N, Donovan M, Woolf B, Robison K, Jeyaseelan R, Breitbart RE, Acton, SA novel angiotensin-converting enzyme-related carboxypeptidase (ACE2) converts angiotensin I to angiotensin 1–9. Circ Res. 2002; 87: 1–9.
32.Harmer D, Gilbert M, Borman R, Clark KL. Quantitative mRNA expression profiling of ACE 2, a novel homologue of angiotensin converting enzyme. FEBS Lett. 2002; 532: 107–110.
33. Komatsu T, Suzuki Y, Imai J, Sugano S, Hida M, Tanigami A, Muroi S, Yamada Y, Hanaoka KK. Molecular cloning, mRNA expression and chromosomal localization of mouse angiotensin-converting enzyme-related carboxypeptidase (mACE2). DNA Seq. 2002; 13: 217–220.
34.Huang L, Sexton DL, Skogerson K, Devlin M, Smith R, Sanyal I, Parry T, Kent R, Enright J, Wu Q-L, Conley G, DeOliveira D, Morganelli L, Ducar M, Wescott CR, Ladner RC. Novel peptide inhibitors of angiotensin-converting enzyme 2. J Biol Chem. 2003; 278: 15532–15540.
35. Carlos M. Ferrario, Aaron J. Trask, and Jewell A. Jessup.Advances in biochemical and functional roles of angiotensin-converting enzyme 2 and angiotensin-(1–7) in regulation of cardiovascular function. Am J Physiol Heart Circ Physiol. 2005;289: 2281-2290.
36. Raizada MK, Ferreira AJ. ACE2: a new target for cardiovascular disease therapeutics. J Cardiovasc Pharmacol. 2007 Aug;50(2):112-119.
37. Julie R. ACE2: A New Target for Prevention of Diabetic Nephropathy? J Am Soc Nephrol 2006;17: 2957-2959.
38. Fletcher EC. Sympathetic over activity in the etiology of hypertension of obstructive sleep apnea. Sleep 2003;26:15–19.
39. Phillips BG, Somers VK. Hypertension and obstructive sleep apnea. Curr Hypertens Rep 2003;5:380–385.
40. Sharabi Y, Dagan Y, Grossman E. Sleep apnea as a risk factor for hypertension. Curr Opin Nephrol Hypertens 2004;13:359–364.
41.Fletcher EC, Bao G, Li R. Renin activity and blood pressure in response to chronic episodic hypoxia. Hypertension 1999;34:309–314.
42. Moller DS, Lind P, Strunge B, Pedersen EB. Abnormal vasoactive hormones and 24-hour blood pressure in obstructive sleep apnea. Am J Hypertens 2003;16:274–280.
43. Barcelo A, Elorza MA, Barbe F, Santos C, Mayoralas LR, Agusti AG. Angiotensin converting enzyme in patients with sleep apnoea syndrome: plasma activity and genepolymorphisms. Eur Respir J 2001;17:728–732.
44. Rigat B, Hubert C, Alhenc-Gelas F, Cambien F, Corvol P, Soubrier F. An insertion/deletion polymorphism in the angiotensin I-converting enzyme gene accounting for half the variance of serum enzyme levels. J Clin Invest 1990;86:1343–1346.
45. Busjahn A, Knoblauch H, Knoblauch M, Bohlender J, Menz M, Faulhaber HD, Becker A, Schuster H, Luft FC. Angiotensin-converting enzyme and angiotensinogen gene polymorphisms, plasma levels, cardiac dimensions: a twin study. Hypertension 1997;29:165–170.
46. Agerholm-Larsen B, Nordestgaard BG, Tybjaerg-Hansen A. ACE gene polymorphism in cardiovascular disease: meta-analyses of small and large studies in whites. Arterioscler Thromb Vasc Biol 2000;20:484–492.
47. Jalil JE, Piddo AM, Cordova S, Chamorro G, Braun S, Jalil R, Vega J, Jadue PL, Lavandero S, Lastra P. Prevalence of the angiotensin I converting enzyme insertion/deletion polymorphism, plasma angiotensin converting enzyme activity, and left ventricular mass in a normotensive Chilean population. Am J Hypertens 1999;12:697–704.
48.Ling Lin, Laurel Finn, Jing Zhang, Terry Young and Emmanuel Mignot.Angiotensin-converting Enzyme, Sleep-disordered Breathing, and Hypertension. American Journal of Respiratory and Critical Care Medicine 2004;170.1349-1353.
49.Morrell NW, Danilov SM, Satyan KB, Morris KG, Stenmark KR.Right ventricular angiotensin converting enzyme activity and expression is increased during hypoxic pulmonary hypertension. Cardiovasc Res. 1997 May;34(2):393-403.
50. Morrell NW, Atochina EN, Morris KG, Danilov SM, Stenmark KR.Angiotensin converting enzyme expression is increased in small pulmonary arteries of rats with hypoxia-induced pulmonary hypertension. J Clin Invest. 1995 Oct;96(4):1823-1833.
51. Kay JM, Keane PM, Suyama KL, Gauthier D.Lung angiotensin converting enzyme activity in chronically hypoxic rats. Thorax. 1985 Aug;40(8):587-591.
52. Zhang R, Wu Y, Zhao M, Liu C, Zhou L, Shen S, Liao S, Yang K, Li Q, Wan H. Role of HIF-1alpha in the regulation ACE and ACE2 expression in hypoxic human pulmonary artery smooth muscle cells. Am J Physiol Lung Cell Mol Physiol. 2009Oct;297(4):631-640.
53. Hoffmann S, Krause T, van Geel PP, Willenbrock R, Pagel I, Pinto Y, Buikema H, van Gilst WH, Lindschau C, Paul M, Inagami T, Ganten D, and Urata H. Overexpression of the human angiotensin II type 1 receptor in the rat heart augments load induced cardiac hypertrophy. J Mol Med 2001 (79): 601–608.
54.Gray MO, Long CS, Kalinyak JE, Li HT, and Karliner JS. Angiotensin II stimulates cardiac myocyte hypertrophy via paracrine release of TGF-beta 1 and endothelin-1 from fibroblasts. Cardiovasc Res 1998(40): 352–363.
55. Schunkert H, Jackson B, Tang SS, Schoen FJ, Smits JFM, Apstein CS, and Lorell BH. Distribution and functional relevance of cardiac angiotensin converting enzyme in hypertrophied rat hearts. Circulation 1993( 87): 1328–1339.
56.Rothermund L, Pinto YM, Vetter R, Herfort N, Kossmehl P, Neumayer HH, Paul M, and Kreutz R. Effects of angiotensin II subtype 1 receptor blockade on cardiac fibrosis and sarcoplasmic reticulum Ca2+ handling in hypertensive transgenic rats overexpressing the Ren2 gene. J Hypertens 2001(19): 1465–1472.
57.Rothermund L, Pinto YM, Hocher B, Vetter R, Leggewie S, Kobetamehl P, Orzechowski HD, Kreutz R, and Paul M. Cardiac endothelin system impairs left ventricular function in renin-dependent hypertension via decreased sarcoplasmic reticulum Ca2+ uptake. Circulation 2000( 102): 1582–1588.
58. Malhotra R, Sadoshima J, Brosius F, and Izumo S. Mechanical stretch and angiotensin II differentially upregulate the renin-angiotensin-system in cardiac myocytes in vitro. Circ Res 1999(85): 137–146.
59. Sadoshima J, Xu Y, Slayter H, and Izumo S. Autocrine release of angiotensin II mediates stretch-induced hypertrophy of cardiac myocytes in vitro. Cell 1993(75): 977–984.
60. Leri A, Claudio PP, Li Q, Wang X, Reiss K, Wang S, Malhotra A, Kajstura J, and Anversa P. Stretch-mediated release of angiotensin II induces myocyte apoptosis by activating p53 that enhances the local renin-angiotensin system and decreases the Bcl-2-to-Bax protein ratio in the cell. J Clin Invest 1998(101): 1326–1342.
61. Kojima M, Shiojima I, Yamazaki T, Komuro I, Zou Z, Wang Y, Mizuno T, Ueki K,Tobe K, and Kadowaki T. Angiotensin II receptor antagonist TCV-116 induces regression of hypertensive left ventricular hypertrophy in vivo and inhibits the intracellular signaling pathway of stretch-mediated cardiomyocyte hypertrophy in vitro. Circulation 1994( 89): 2204–2211.
62. Senbonmatsu T, Ichihara S, Price E Jr, Gaffney FA, and Inagami T. Evidence for angiotensin II type 2 receptor-mediated cardiac myocyte enlargement during in vivo pressure overload. J Clin Invest 2000(106): 25–29.
63.Hirsch AT, Talsness CE, Schunkert H, Paul M, and Dzau VJ. Tissue-specific activation of cardiac angiotensin converting enzyme in experimental heart failure. Circ Res 1991(69): 475–482.
64.Pinto YM, Pinto-Sietsma SJ, Philipp T, Engler S, Kossamehl P, Hocher B, Marquardt H, Sethmann S, Lauster R, Merker HJ, and Paul M. Reduction in left ventricular messenger RNA for transforming growth factor beta(1) attenuates left ventricular fibrosis and improves survival without lowering blood pressure in the hypertensive TGR(mRen2)27 Rat. Hypertension 2000(36): 747–754.
65. Nunohiro T, Ashizawa N, Graf K, Do YS, Hsueh WA, and Yano K. Angiotensin II promotes remodelling-related events in cardiac fibroblasts. Heart Vessels Suppl 1997(12): 201–204.
66. Cigola E, Kajstura J, Li B, Meggs LG, and Anversa P. Angiotensin II activates programmed myocyte cell death in vitro. Exp Cell Res1997 ;231: 363–371.
67. Anversa P, Cheng W, Liu Y, Leri A, Redaelli G, and Kajstura J. Apoptosis and myocardial infarction. Basic Res Cardiol 93 Suppl 1998(3): 8–12.
68. Diez J, Panizo A, Hernandez M, Vega F, Sola I, Fortuno MA, and Pardo J. Cardiomyocyte apoptosis and cardiac angiotensin-converting enzyme in spontaneously hypertensive rats. Hypertension1997;30: 1029–1034.
69. Fiordaliso F, Li B, Latini R, Sonnenblick EH, Anversa P, Leri A, and Kajstura J. Myocyte death in streptozotocin-induced diabetes in rats is angiotensin II-dependent. Lab Invest 2000;80: 513–527.
70. Diep QN, El Mabrouk M, Yue P, and Schiffrin EL. Effect of AT(1) receptor blockade on cardiac apoptosis in angiotensin II-induced hypertension. Am J Physiol Heart CircPhysiol 2002;282: 1635–1641.
71. Hein L, Stevens ME, Barsh GS, Pratt RE, Kobilka BK, Dzau VJ. Overexpression of angiotensin AT1 receptor transgene in the mouse myocardium produces a lethal phenotype associated with myocyte hyperplasia and heart block. Proc Natl Acad Sci U S A. 1997; 94: 6391–6396.
72. Dodge SM, Beardslee MA, Darrow BJ, Green KG, Beyer EC, Saffitz JE. Effects of angiotensin II on expression of the gap junction channel protein connexin43 in neonatal rat ventricular myocytes. J Am Coll Cardiol. 1998 Sep;32(3):800-807.
73. De Mello WC, Cherry RC, Manivannann S. Electrophysiologic and morphologic abnormalities in the failing heart: effect of enalapril on the electrical properties. J Card Fail. 1997; 3: 53–61.
74. De Mello WC. Cell coupling and impulse propagation in the failing heart. J Cardiovasc Electrophysiol. 1999; 10: 1409–1420.
75. De Mello WC, Crespo MJ. Correlation between changes in morphology, electrical properties, and angiotensin-converting enzyme activity in the failing heart. Eur J Pharmacol. 1999; 378: 187–194.
76. Crackower MA, Sarao R, Oudit GY, Yagil C, Kozieradzki I, Scanga SE, Oliveira- dos-Santos AJ, da Costa J,Zhang L, Pei Y, Scholey J, Ferrario CM, Manoukian AS, Chappell MC, Backx PH, Yagil Y, Penninger JM:Angiotensin- converting enzyme 2 is an essential regulator of heart function. Nature 2002, 417:822-828.
77. Zisman LS, Keller RS, Weaver B, Lin Q, Speth R,Bristow MR, Canver CC. Increased angiotensin-(1-7)-forming activity in failing human heart ventricles:evidence for upregulation of the angiotensin-converting enzyme Homologue ACE2. Circulation. 2003;108:1707-1712.
78.Crackower MA, Sarao R, Oudit GY, Yagil C, Kozieradzki I, Scanga SE, Oliveira-Dos-Santos AJ, Da Costa J, Zhang L, Pei Y, Scholey J, Ferrario CM, Manoukian AS, Chappell MC, Backx PH, Yagil Y, Penninger JM. Angiotensin-converting enzyme 2 is an essential regulator of heart function. Nature. 2002; 417: 822–828.
79. Fiona J. Warner, Rebecca A. Lew, A. Ian Smith,Daniel W. Lambert, Nigel M. Hooper,and Anthony J.Turner: Angiotensin-converting Enzyme 2 (ACE2), But Not ACE, Is Preferentially Localized to the Apical Surface of Polarized Kidney Cells. THE JOURNAL OF BIOLOGICAL CHEMISTRY VOL. 2005(47);280; 39353-39362.
80. Zisman LS, Keller RS, Weaver B, Lin Q, Speth R, Bristow MR, Canver CC. Increased angiotensin-(1–7)-forming activity in failing human heart ventricles. Evidence for upregulation of the angiotensin-converting enzyme homologue ACE2. Circulation. 2003 Oct 7;108(14):1707-12.
81. Goulter A, Goddard MJ, Allen JC, Clark KL. ACE2 gene expression is up-regulated in the human failing heart. 2004 May 19;2-19.
82.Johnston CI Tissue angiotensin converting enzyme in cardiac and vascular hypertrophy, repair, and remodeling. Hypertension. 1994; 23: 258–268.
83. Ferrario CM, Trask AJ, Jessup JA. Advances in the biochemical and functional roles of angiotensin converting enzyme 2 and angiotensin-(1–7) in the regulation of cardiovascular function. Am J Physiol Heart Circ Physiol. 2005; 289: 2281–2290.
84. De Mello WC, Cherry RC, Manivannann S. Electrophysiologic and morphologic abnormalities in the failing heart: effect of enalapril on the electrical properties. J Card Fail. 1997; 3: 53–61.
85.Ferrario CM, Trask AJ, Jessup JA. Advances in biochemical and functional roles of angiotensin-converting enzyme 2 and angiotensin-(1-7) in regulation of cardiovascular function. Am J Physiol. 2005;289:2281–2290.
86. Iwata M, Cowling RT, Gurantz D, et al. Angiotensin-(1-7) binds to specific receptors on cardiac fibroblasts to initiate antifibrotic and antitrophic effects. Am J Physiol. 2005;289:2356–2363.
87.Tom B, de Vries R, Saxena PR, et al. Bradykinin potentiation by angiotensin-(1-7) and ACE inhibitors correlates with ACE C- and Ndomain blockade. Hypertension. 2001;38:95–99.
88.Ferreira AJ, Santos RA, and Almeida AP. Angiotensin-(1–7): cardioprotective effect in myocardial ischemia/reperfusion. Hypertension 2001;38: 665–668.
89. Ferreira AJ, Santos RA, and Almeida AP. Angiotensin-(1–7) improves the post-ischemic function in isolated perfused rat hearts. Braz J Med Biol Res 2002;35:1083–1090.
90. De Mello WC. Angiotensin (1–7) re-establishes impulse conduction in cardiac muscle during ischaemia-reperfusion. The role of the sodium pump. J Renin Angiotensin Aldosterone Syst 2004(5): 203–208.
91.Ferrario CM, Jessup J, Chappell MC, et al. Effect of angiotensin-converting enzyme inhibition and angiotensin II receptor blockers on cardiac angiotensin-converting enzyme 2. Circulation. 2005;111:2605–2610.
92.Seyedi N, Xu X, Nasjletti A, et al. Coronary kinin generation mediates nitric oxide release after angiotensin receptor stimulation. Hypertension. 1995;26:164–70.
93. Liu YH, Yang XP, Sharov VG, et al. Effects of angiotensin-converting enzyme inhibitors and angiotensin II type 1 receptor antagonists in rats with heart failure. Role of kinins and angiotensin II type 2 receptors. J Clin Invest. 1997;99:1926–35.
94.Jugdutt BI, Xu Y, Balghith M, et al. Cardioprotection induced by AT1R blockade after reperfused myocardial infarction: association with regional increase in AT2R, IP3R and PKC proteins and cGMP. J Cardiovasc Pharmacol Ther. 2000;5:301–311.
95. Xu Y, Menon V, Jugdutt BI. Cardioprotection after angiotensin II type 1 blockade involves angiotensin II type 2 receptor expression and activation of protein kinase C-epsilon in acutely reperfused myocardial infarction in the dog. Effect of UP269-6 and losartan on AT1 and AT2-receptor expression and IP3 receptor and PKCe proteins. J Renin Angiotensin Aldosterone Syst. 2000;1:184–195.
96. Jugdutt BI, Balghith M. Enhanced regional AT2-receptor and PKC expression during cardioprotection induced by AT1-receptor blockade after reperfused myocardial infarction. J Renin Angiotensin Aldosterone Syst. 2001;2:134–140.
97.Campbell DJ, Krum H, Esler MD. Losartan increases bradykinin levels in hypertensive humans. Circulation. 2005;111:315–20.
98. Ishiyama Y, Gallagher PE, Averill DB, Tallant EA, Brosnihan KB, and Ferrario CM. Upregulation of angiotensin-converting enzyme 2 after myocardial infarction by blockade of angiotensin II receptors. Hypertension 2004;43: 970–976.
2. Van Kats JP, Danser AH, van Meegen J, Verdouw PD, and Schalekamp MA. Angiotensin production by the heart: a quantitative study in pigs with the use of radiolabeled angiotensin infusions. Circulation 98: 73–81.
3. Nagai N, Oike Y, Noda K, Urano T, Kubota Y, Ozawa Y, Shinoda H, Koto T, Shinoda K, Inoue M, Tsubota K, Yamashiro K, Suda T, Ishida S. Suppression of ocular inflammation in endotoxin-induced uveitis by blocking the angiotensin II type 1 receptor. Invest Ophthalmol Vis Sci. 2005 Aug;46(8):2925-2931.
4. Glen E. Foster, Marc J. Poulin , Patrick J. Hanly. Intermittent hypoxia and vascular function: implications for obstructive sleep apnoea. Experimental Physiology 92(1); 51-65.
5. Tasali E, Ip MS. Obstructive sleep apnea and metabolic syndrome: alterations in glucose metabolism and inflammation. Proc Am Thorac Soc. 2008 Feb 15;5(2):207-217.
6. Fletcher EC, Lesske J, Qian W, et al. Episodic hypoxia causes diurnal elevation of systemic blood pressure in rats. Hypertension, 1992, 19:555-561.
7.陈晓阳,曾奕明,黄子扬,陶耕,郑兴中,李永加.慢性间断缺氧小鼠缺氧诱导因子1α的研究.中华结核和呼吸杂志.2005;28(2):93-96.
8.宋爱玲,曾奕明,陈晓阳.慢性缺氧/再氧合小鼠模型实验研究.国际呼吸杂志.2006;26(6):408-411.
9. Yuan ZM, Chen BY, Wang PX, Li SY, Chen YL, Dong LX. Changes of angiotensin II and its receptor during the development of chronic intermittent hypoxia-induced hypertension in rats. Zhonghua Jie He He Hu Xi Za Zhi. 2004 Sep;27(9):577-580.
10.Carey RM, Siragy HM. Newly recognized components of the renin-angiotensin system: potential role in cardiovascular and renal regulation. Endocr Rev. 2005; 24: 261–271.
11. Pagliaro P, Penn C. Rethinking the rennin-Angiotensisn system and its role in cardiovascular regulation. Cardiovasc Drugs Ther. 2005; 19: 77–87.
12. Yamada HF, Fabris B, Allen AM, Jackson B, Johnston CI, Mendelsohn AO.Localization of angiotensin converting enzyme in rat heart. Circ Res. 1991; 68: 141–149.
13. Martin Paul, Ali Poyan Mehr and Reinhold Kreutz. Physiology of Local Renin-Angiotensin Systems. Physiol. Rev. 2006;86: 747-803.
14.De Mello WC, Cherry RC, Manivannann S. Electrophysiologic and morphologic abnormalities in the failing heart: effect of enalapril on the electrical properties. J Card Fail. 1997; 3: 53–61.
15. De Mello WC. Cell coupling and impulse propagation in the failing heart. J Cardiovasc Electrophysiol. 1999; 10: 1409–1420.
16. De Mello WC, Crespo MJ. Correlation between changes in morphology, electrical properties, and angiotensin-converting enzyme activity in the failing heart. Eur J Pharmacol. 1999; 378: 187–194.
17.Lam SY, Fung ML, Leung PS.Regulation of the angiotensin -converting enzyme activity by a time-course hypoxia in the carotid body. J Appl Physiol 2004,96: 809-813.
18. Morrell NW, Danilov SM, Satyan KB, Morris KG, Stenmark KR.Right ventricular angiotensin converting enzyme activity and expression is increased during hypoxic pulmonary hypertension. Cardiovasc Res. 1997 May;34(2):393-403.
19. Morrell NW, Atochina EN, Morris KG, Danilov SM, Stenmark KR.Angiotensin converting enzyme expression is increased in small pulmonary arteries of rats with hypoxia-induced pulmonary hypertension. J Clin Invest. 1995 Oct;96(4):1823-1833.
20. Kay JM, Keane PM, Suyama KL, Gauthier D.Lung angiotensin converting enzyme activity in chronically hypoxic rats. Thorax. 1985 Aug;40(8):587-591.
21.Davidson D, Stalcup SA, Mellins RB. Angiotensin-converting enzyme activity and its modulation by oxygen tension in the guinea pig fetal-placental unit. Circ Res. 1981 Feb;48(2):286-291.
22. Vijay Koka,Xiao Ru Huang,Arthur C.K. Chung,WanshengWang,Luan D. Truong, and Hui Yao Lan. Angiotensin II Up-Regulates Angiotensin I Converting Enzyme (ACE), but Down-Regulates ACE2 via the AT1-ERK/p38 MAP Kinase Pathway. The American Journal of Pathology, 2008 May;172(5): 1174–1183.
23.钟毅,李家富. ANG(1- 7)与高血压保护作用.中国心血管病研究2008;6(9):702-706.
24. Tipnis SR, Hooper NM, Hyde R, Karran E, Christie G, and Turner AJ. A human homolog of angiotensin-converting enzyme. Cloning and functional expression as a captopril-insensitive carboxypeptidase. J Biol Chem. 2000; 275: 33238–33243
25. Donoghue M, Hsieh F, Baronas E, Godbout K, Gosselin M, Stagliano N, Donovan M, Woolf B, Robison K, Jeyaseelan R, Breitbart RE, Acton, SA novel angiotensin-converting enzyme-related carboxypeptidase (ACE2) converts angiotensin I to angiotensin 1–9. Circ Res. 2002; 87: E1–E9.
26.Donoghue M, Hsieh F, Baronas E, et al. A novel angiotensin-converting enzyme-related carboxypeptidase (ACE2) converts angiotensin I to angiotensin 1-9. Circ. Res. 2000;87:E1–E9.
27.Burrell LM, Risvanis J, Kubota E, et al. Myocardial infarction increases ACE2 expression in rat and humans. Eur. Heart J. 2005;26:369–375.
28. Harmer D, Gilbert M, Borman R, Clark KL. Quantitative mRNA expression profiling of ACE 2, a novel homologue of angiotensin converting enzyme. FEBS Lett. 2002; 532: 107–110
29. Komatsu T, Suzuki Y, Imai J, Sugano S, Hida M, Tanigami A, Muroi S, Yamada Y, Hanaoka KK. Molecular cloning, mRNA expression and chromosomal localization of mouse angiotensin-converting enzyme-related carboxypeptidase (mACE2). DNA Seq. 2002; 13: 217–220.
30.Yamamoto K, Ohishi M, Katsuya T, et al. Deletion of Angiotensin-Converting Enzyme 2 Accelerates Pressure Overload-Induced Cardiac Dysfunction by Increasing Local Angiotensin II. Hypertension. 2006;47:718–726.
31.Zisman LS, Keller RS, Weaver B, Lin Q, Speth R, Bristow MR, Canver CC. Increased angiotensin-(1–7)-forming activity in failing human heart ventricles. Evidence for upregulation of the angiotensin-converting enzyme homologue ACE2. Circulation. 2003; 108: 1707.
32. Goulter A, Goddard MJ, Allen JC, Clark KL. ACE2 gene expression is up-regulated in the human failing heart. BMC Med. 2004; 2: 19.
33.Johnston CI Tissue angiotensin converting enzyme in cardiac and vascular hypertrophy, repair, and remodeling. Hypertension. 1994; 23: 258–2680.
34. Ferrario CM, Trask AJ, Jessup JA. Advances in the biochemical and functional roles of angiotensin converting enzyme 2 and angiotensin-(1–7) in the regulation of cardiovascular function. Am J Physiol Heart Circ Physiol. 2005; 289: H2281–H2290.
35. De Mello WC, Cherry RC, Manivannann S. Electrophysiologic and morphologic abnormalities in the failing heart: effect of enalapril on the electrical properties. J Card Fail. 1997; 3: 53–61.
36.Ocaranza MP, Godoy I, Jalil JE, et al. Enalapril Attenuates Downregulation of Angiotensin-Converting Enzyme 2 in the Late Phase of Ventricular Dysfunction in Myocardial Infarcted Rat. Hypertension. 2006;48:572–578.
37. Burchill L, Velkoska E, Dean RG, Lew RA, Smith AI, Levidiotis V, Burrell LM. Acute kidney injury in the rat causes cardiac remodelling and increases angiotensin-converting enzyme 2 expression. Exp. Physiol. 2008;93:622–630.
38.Zhang R, Wu Y, Zhao M, Liu C, Zhou L, Shen S, Liao S, Yang K, Li Q, Wan H. Role of HIF-1alpha in the regulation ACE and ACE2 expression in hypoxic human pulmonary artery smooth muscle cells. Am J Physiol Lung Cell Mol Physiol. 2009 Oct;297(4):631-640.
39.K. KRAMKOWSKI, A. MOGIELNICKI, W. BUCZKO. THE PHYSIOLOGICAL SIGNIFICANCE OF THE ALTERNATIVE PATHWAYS OF ANGIOTENSIN II PRODUCTION. JOURNAL OF PHYSIOLOGY AND PHARMACOLOGY 2006, 57(4): 529-539.
40. Michiya IGASE, Katsuhiko KOHARA, Tokihisa NAGAI, Tetsuro MIKI, Carlos M. FERRARIO. Increased Expression of Angiotensin Converting Enzyme 2 in Conjunction with Reduction of Neointima by Angiotensin II Type 1 Receptor Blockade. Hypertens Res. 2008 Mar;31(3):553-559.
41. Gray MO, Long CS, Kalinyak JE, Li HT, and Karliner JS. Angiotensin II stimulates cardiac myocyte hypertrophy via paracrine release of TGF-beta 1 and endothelin-1 from fibroblasts. Cardiovasc Res 1998(40): 352–363.
42. Hirsch AT, Talsness CE, Schunkert H, Paul M, and Dzau VJ. Tissue-specific activation of cardiac angiotensin converting enzyme in experimental heart failure. Circ Res 1991(69): 475–482.
43.Cigola E, Kajstura J, Li B, Meggs LG, and Anversa P. Angiotensin II activates programmed myocyte cell death in vitro. Exp Cell Res1997 ;231: 363–371.
44. Ferrario CM, Trask AJ, Jessup JA. Advances in biochemical and functional roles of angiotensin-converting enzyme 2 and angiotensin-(1-7) in regulation of cardiovascular function. Am J Physiol. 2005;289:2281–2290.
45.Ferrario CM, Jessup J, Chappell MC, et al. Effect of angiotensin-converting enzyme inhibition and angiotensin II receptor blockers on cardiac angiotensin-converting enzyme 2. Circulation. 2005;111:2605–2610.
46.Joergen O, Dendorfer A, Dominiak P. Cardiovascular and renal function of angiotensin II type-2 receptor. Cardiovascular Res. 2004; 62: 460–467.
47.Rey S, Valdés G, Iturriaga R. Pathophysiology of obstructive sleep apnea-associated hypertension. Rev Med Chil. Epub 2007 Dec 20;135(10):1333-1342.
48. Yuan ZM, Chen BY, Wang PX, Li SY, Chen YL, Dong LX. Changes of angiotensin II and its receptor during the development of chronic intermittent hypoxia-induced hypertension in rats. Zhonghua Jie He He Hu Xi Za Zhi. 2004 Sep;27(9):577-580.
49. Lai CJ, Yang CC, Hsu YY, Lin YN, Kuo TB. Enhanced sympathetic outflow and decreased baroreflex sensitivity are associated with intermittent hypoxia-induced systemic hypertension in conscious rats.J Appl Physiol. 2006 Jun;100(6):1974-1982.
1. Alvarez-Sala Walther JL. Obstructive sleep apnea syndrome.An R Acad Nac Med (Madr). 2002;119(1):197-211.
2. Glen E. Foster, Marc J. Poulin , Patrick J. Hanly. Intermittent hypoxia and vascular function: implications for obstructive sleep apnoea. Experimental Physiology 92(1):51-65.
3. Tasali E, Ip MS. Obstructive sleep apnea and metabolic syndrome: alterations in glucose metabolism and inflammation. Proc Am Thorac Soc. 2008 Feb 15;5(2):207-217.
4. Rey S, Valdés G, Iturriaga R. Pathophysiology of obstructive sleep apnea-associated hypertension. Rev Med Chil. Epub 2007 Dec 20;135(10):1333-1342.
5. Yuan ZM, Chen BY, Wang PX, Li SY, Chen YL, Dong LX. Changes of angiotensin II and its receptor during the development of chronic intermittent hypoxia-induced hypertension in rats. Zhonghua Jie He He Hu Xi Za Zhi. 2004 Sep;27(9):577-580.
6. Eugene C. Fletcher. Physiological and Genomic Consequences of Intermittent Hypoxia Invited Review: Physiological consequences of intermittent hypoxia: systemic blood pressure. J Appl Physiol 2001(90): 1600-1605.
7. Lai CJ, Yang CC, Hsu YY, Lin YN, Kuo TB. Enhanced sympathetic outflow and decreased baroreflex sensitivity are associated with intermittent hypoxia-induced systemic hypertension in conscious rats.J Appl Physiol. 2006 Jun;100(6):1974-1982.
8. Prabhakar NR. Oxygen sensing during intermittent hypoxia: cellular and molecular mechanisms. J Appl Physiol. 2001 May;90(5):1986-1994.
9.陈晓阳,曾奕明,黄子扬,陶耕,郑兴中,李永加.慢性间断缺氧小鼠缺氧诱导因子1α的研究.中华结核和呼吸杂志.2005;28(2):93-96.
10. Jurkovicova I, Celec P, Mucska I, Hodosy J. On the origin of cardiovascular complications of sleep apnea syndrome by the means of molecular interactions. Bratisl Lek Listy. 2003;104(4-5):167-173.
11. Chen L, Einbinder E, Zhang Q, Hasday J, Balke CW, Scharf SM. Oxidative stress and left ventricular function with chronic intermittent hypoxia in rats.Am J Respir Crit Care Med. 2005 Oct 1;172(7):915-20.
12. Chao J, Wood JG, Gonzalez NC. Alveolar hypoxia, alveolar macrophages, and systemic inflammation. Respir Res. 2009 (22);10-54.
13. Sun J, Sukhova GK, Yang M, Wolters PJ, MacFarlane LA, Libby P, Sun C, Zhang Y, Liu J, Ennis TL, Knispel R, Xiong W, Thompson RW, Baxter BT, Shi GP. Mast cells modulate the pathogenesis of elastase-induced abdominal aortic aneurysms in mice. J Clin Invest. 2007 Nov;117(11):3359-3368.
14. Neri Serneri GG, Boddi M, Modesti PA, Coppo M, Cecioni I, Toscano T, Papa ML, Bandinelli M, Lisi GF, Chiavarelli M. Cardiac angiotensin II participates in coronary microvessel inflammation of unstable angina and strengthens the immunomediated component. Circ Res. 2004 25;94(12):1630-1637.
15. Wolf G. Free radical production and angiotensin. Curr Hypertens Rep. 2002; 2: 167–173.
16. Morgan BJ. Vascular consequences of intermittent hypoxia. Adv Exp Med Biol. 2007;618:69-84.
17.Van Kats JP, Danser AH, van Meegen J, Verdouw PD, and Schalekamp MA. Angiotensin production by the heart: a quantitative study in pigs with the use of radiolabeled angiotensin infusions. Circulation 1998(98): 73–81.
18.王云英,王培林. ACE及其基因多态性与心脏间质病.国外医学遗传学分册2004; 27(1): 27-30.
19. Carey RM, Siragy HM. Newly recognized components of the renin-angiotensin system: potential role in cardiovascular and renal regulation. Endocr Rev. 2005; 24: 261–271.
20. Pagliaro P, Penn C. Rethinking the rennin-Angiotensisn system and its role in cardiovascular regulation. Cardiovasc Drugs Ther. 2005; 19: 77–87.
21.Yamada HF, Fabris B, Allen AM, Jackson B, Johnston CI, Mendelsohn AO. Localization of angiotensin converting enzyme in rat heart. Circ Res. 1991; 68: 141–149.
22. Martin Paul, Ali Poyan Mehr and Reinhold Kreutz. Physiology of Local Renin-Angiotensin Systems. Physiol. Rev. 86: 747-803.
23. Deddish PA, Marcic B, Jackman HL, Wang HZ, Skidgel RA, Erdos EG. N-domain-specific substrate and C-domain inhibitors of angiotensin-converting enzyme: angiotensin-(1–7) and keto-ACE. Hypertension. 1998; 31: 912–917.
24.钟毅,李家富. ANG(1- 7)与高血压保护作用.中国心血管病研究2008;6(9):702-706.
25. Inagami T. The renin angiotensin system. Essays Biochem. 1994; 28: 147–164.
26.K. KRAMKOWSKI, A. MOGIELNICKI, W. BUCZKO. THE PHYSIOLOGICAL SIGNIFICANCE OF THE ALTERNATIVE PATHWAYS OF ANGIOTENSIN II PRODUCTION. JOURNAL OF PHYSIOLOGY AND PHARMACOLOGY 2006, 57(4): 529-539.
27.Michiya IGASE, Katsuhiko KOHARA, Tokihisa NAGAI, Tetsuro MIKI, Carlos M. FERRARIO. Increased Expression of Angiotensin Converting Enzyme 2 in Conjunction with Reduction of Neointima by Angiotensin II Type 1 Receptor Blockade. Hypertens Res. 2008 Mar;31(3):553-559.
28.Joergen O, Dendorfer A, Dominiak P. Cardiovascular and renal function of angiotensin II type-2 receptor. Cardiovascular Res. 2004; 62: 460–467.
29.Levy BI. Can angiotensin II type 2 receptors have deleterious effects in cardiovascular disease? Implications for therapeutic blockade of the renin-angiotensin system. Circulation. 2004;109:8–13.
30. Tipnis SR, Hooper NM, Hyde R, Karran E, Christie G, and Turner AJ. A human homolog of angiotensin-converting enzyme. Cloning and functional expression as a captopril-insensitive carboxypeptidase. J Biol Chem. 2000; 275: 33238–33243
31. Donoghue M, Hsieh F, Baronas E, Godbout K, Gosselin M, Stagliano N, Donovan M, Woolf B, Robison K, Jeyaseelan R, Breitbart RE, Acton, SA novel angiotensin-converting enzyme-related carboxypeptidase (ACE2) converts angiotensin I to angiotensin 1–9. Circ Res. 2002; 87: 1–9.
32.Harmer D, Gilbert M, Borman R, Clark KL. Quantitative mRNA expression profiling of ACE 2, a novel homologue of angiotensin converting enzyme. FEBS Lett. 2002; 532: 107–110.
33. Komatsu T, Suzuki Y, Imai J, Sugano S, Hida M, Tanigami A, Muroi S, Yamada Y, Hanaoka KK. Molecular cloning, mRNA expression and chromosomal localization of mouse angiotensin-converting enzyme-related carboxypeptidase (mACE2). DNA Seq. 2002; 13: 217–220.
34.Huang L, Sexton DL, Skogerson K, Devlin M, Smith R, Sanyal I, Parry T, Kent R, Enright J, Wu Q-L, Conley G, DeOliveira D, Morganelli L, Ducar M, Wescott CR, Ladner RC. Novel peptide inhibitors of angiotensin-converting enzyme 2. J Biol Chem. 2003; 278: 15532–15540.
35. Carlos M. Ferrario, Aaron J. Trask, and Jewell A. Jessup.Advances in biochemical and functional roles of angiotensin-converting enzyme 2 and angiotensin-(1–7) in regulation of cardiovascular function. Am J Physiol Heart Circ Physiol. 2005;289: 2281-2290.
36. Raizada MK, Ferreira AJ. ACE2: a new target for cardiovascular disease therapeutics. J Cardiovasc Pharmacol. 2007 Aug;50(2):112-119.
37. Julie R. ACE2: A New Target for Prevention of Diabetic Nephropathy? J Am Soc Nephrol 2006;17: 2957-2959.
38. Fletcher EC. Sympathetic over activity in the etiology of hypertension of obstructive sleep apnea. Sleep 2003;26:15–19.
39. Phillips BG, Somers VK. Hypertension and obstructive sleep apnea. Curr Hypertens Rep 2003;5:380–385.
40. Sharabi Y, Dagan Y, Grossman E. Sleep apnea as a risk factor for hypertension. Curr Opin Nephrol Hypertens 2004;13:359–364.
41.Fletcher EC, Bao G, Li R. Renin activity and blood pressure in response to chronic episodic hypoxia. Hypertension 1999;34:309–314.
42. Moller DS, Lind P, Strunge B, Pedersen EB. Abnormal vasoactive hormones and 24-hour blood pressure in obstructive sleep apnea. Am J Hypertens 2003;16:274–280.
43. Barcelo A, Elorza MA, Barbe F, Santos C, Mayoralas LR, Agusti AG. Angiotensin converting enzyme in patients with sleep apnoea syndrome: plasma activity and genepolymorphisms. Eur Respir J 2001;17:728–732.
44. Rigat B, Hubert C, Alhenc-Gelas F, Cambien F, Corvol P, Soubrier F. An insertion/deletion polymorphism in the angiotensin I-converting enzyme gene accounting for half the variance of serum enzyme levels. J Clin Invest 1990;86:1343–1346.
45. Busjahn A, Knoblauch H, Knoblauch M, Bohlender J, Menz M, Faulhaber HD, Becker A, Schuster H, Luft FC. Angiotensin-converting enzyme and angiotensinogen gene polymorphisms, plasma levels, cardiac dimensions: a twin study. Hypertension 1997;29:165–170.
46. Agerholm-Larsen B, Nordestgaard BG, Tybjaerg-Hansen A. ACE gene polymorphism in cardiovascular disease: meta-analyses of small and large studies in whites. Arterioscler Thromb Vasc Biol 2000;20:484–492.
47. Jalil JE, Piddo AM, Cordova S, Chamorro G, Braun S, Jalil R, Vega J, Jadue PL, Lavandero S, Lastra P. Prevalence of the angiotensin I converting enzyme insertion/deletion polymorphism, plasma angiotensin converting enzyme activity, and left ventricular mass in a normotensive Chilean population. Am J Hypertens 1999;12:697–704.
48.Ling Lin, Laurel Finn, Jing Zhang, Terry Young and Emmanuel Mignot.Angiotensin-converting Enzyme, Sleep-disordered Breathing, and Hypertension. American Journal of Respiratory and Critical Care Medicine 2004;170.1349-1353.
49.Morrell NW, Danilov SM, Satyan KB, Morris KG, Stenmark KR.Right ventricular angiotensin converting enzyme activity and expression is increased during hypoxic pulmonary hypertension. Cardiovasc Res. 1997 May;34(2):393-403.
50. Morrell NW, Atochina EN, Morris KG, Danilov SM, Stenmark KR.Angiotensin converting enzyme expression is increased in small pulmonary arteries of rats with hypoxia-induced pulmonary hypertension. J Clin Invest. 1995 Oct;96(4):1823-1833.
51. Kay JM, Keane PM, Suyama KL, Gauthier D.Lung angiotensin converting enzyme activity in chronically hypoxic rats. Thorax. 1985 Aug;40(8):587-591.
52. Zhang R, Wu Y, Zhao M, Liu C, Zhou L, Shen S, Liao S, Yang K, Li Q, Wan H. Role of HIF-1alpha in the regulation ACE and ACE2 expression in hypoxic human pulmonary artery smooth muscle cells. Am J Physiol Lung Cell Mol Physiol. 2009Oct;297(4):631-640.
53. Hoffmann S, Krause T, van Geel PP, Willenbrock R, Pagel I, Pinto Y, Buikema H, van Gilst WH, Lindschau C, Paul M, Inagami T, Ganten D, and Urata H. Overexpression of the human angiotensin II type 1 receptor in the rat heart augments load induced cardiac hypertrophy. J Mol Med 2001 (79): 601–608.
54.Gray MO, Long CS, Kalinyak JE, Li HT, and Karliner JS. Angiotensin II stimulates cardiac myocyte hypertrophy via paracrine release of TGF-beta 1 and endothelin-1 from fibroblasts. Cardiovasc Res 1998(40): 352–363.
55. Schunkert H, Jackson B, Tang SS, Schoen FJ, Smits JFM, Apstein CS, and Lorell BH. Distribution and functional relevance of cardiac angiotensin converting enzyme in hypertrophied rat hearts. Circulation 1993( 87): 1328–1339.
56.Rothermund L, Pinto YM, Vetter R, Herfort N, Kossmehl P, Neumayer HH, Paul M, and Kreutz R. Effects of angiotensin II subtype 1 receptor blockade on cardiac fibrosis and sarcoplasmic reticulum Ca2+ handling in hypertensive transgenic rats overexpressing the Ren2 gene. J Hypertens 2001(19): 1465–1472.
57.Rothermund L, Pinto YM, Hocher B, Vetter R, Leggewie S, Kobetamehl P, Orzechowski HD, Kreutz R, and Paul M. Cardiac endothelin system impairs left ventricular function in renin-dependent hypertension via decreased sarcoplasmic reticulum Ca2+ uptake. Circulation 2000( 102): 1582–1588.
58. Malhotra R, Sadoshima J, Brosius F, and Izumo S. Mechanical stretch and angiotensin II differentially upregulate the renin-angiotensin-system in cardiac myocytes in vitro. Circ Res 1999(85): 137–146.
59. Sadoshima J, Xu Y, Slayter H, and Izumo S. Autocrine release of angiotensin II mediates stretch-induced hypertrophy of cardiac myocytes in vitro. Cell 1993(75): 977–984.
60. Leri A, Claudio PP, Li Q, Wang X, Reiss K, Wang S, Malhotra A, Kajstura J, and Anversa P. Stretch-mediated release of angiotensin II induces myocyte apoptosis by activating p53 that enhances the local renin-angiotensin system and decreases the Bcl-2-to-Bax protein ratio in the cell. J Clin Invest 1998(101): 1326–1342.
61. Kojima M, Shiojima I, Yamazaki T, Komuro I, Zou Z, Wang Y, Mizuno T, Ueki K,Tobe K, and Kadowaki T. Angiotensin II receptor antagonist TCV-116 induces regression of hypertensive left ventricular hypertrophy in vivo and inhibits the intracellular signaling pathway of stretch-mediated cardiomyocyte hypertrophy in vitro. Circulation 1994( 89): 2204–2211.
62. Senbonmatsu T, Ichihara S, Price E Jr, Gaffney FA, and Inagami T. Evidence for angiotensin II type 2 receptor-mediated cardiac myocyte enlargement during in vivo pressure overload. J Clin Invest 2000(106): 25–29.
63.Hirsch AT, Talsness CE, Schunkert H, Paul M, and Dzau VJ. Tissue-specific activation of cardiac angiotensin converting enzyme in experimental heart failure. Circ Res 1991(69): 475–482.
64.Pinto YM, Pinto-Sietsma SJ, Philipp T, Engler S, Kossamehl P, Hocher B, Marquardt H, Sethmann S, Lauster R, Merker HJ, and Paul M. Reduction in left ventricular messenger RNA for transforming growth factor beta(1) attenuates left ventricular fibrosis and improves survival without lowering blood pressure in the hypertensive TGR(mRen2)27 Rat. Hypertension 2000(36): 747–754.
65. Nunohiro T, Ashizawa N, Graf K, Do YS, Hsueh WA, and Yano K. Angiotensin II promotes remodelling-related events in cardiac fibroblasts. Heart Vessels Suppl 1997(12): 201–204.
66. Cigola E, Kajstura J, Li B, Meggs LG, and Anversa P. Angiotensin II activates programmed myocyte cell death in vitro. Exp Cell Res1997 ;231: 363–371.
67. Anversa P, Cheng W, Liu Y, Leri A, Redaelli G, and Kajstura J. Apoptosis and myocardial infarction. Basic Res Cardiol 93 Suppl 1998(3): 8–12.
68. Diez J, Panizo A, Hernandez M, Vega F, Sola I, Fortuno MA, and Pardo J. Cardiomyocyte apoptosis and cardiac angiotensin-converting enzyme in spontaneously hypertensive rats. Hypertension1997;30: 1029–1034.
69. Fiordaliso F, Li B, Latini R, Sonnenblick EH, Anversa P, Leri A, and Kajstura J. Myocyte death in streptozotocin-induced diabetes in rats is angiotensin II-dependent. Lab Invest 2000;80: 513–527.
70. Diep QN, El Mabrouk M, Yue P, and Schiffrin EL. Effect of AT(1) receptor blockade on cardiac apoptosis in angiotensin II-induced hypertension. Am J Physiol Heart CircPhysiol 2002;282: 1635–1641.
71. Hein L, Stevens ME, Barsh GS, Pratt RE, Kobilka BK, Dzau VJ. Overexpression of angiotensin AT1 receptor transgene in the mouse myocardium produces a lethal phenotype associated with myocyte hyperplasia and heart block. Proc Natl Acad Sci U S A. 1997; 94: 6391–6396.
72. Dodge SM, Beardslee MA, Darrow BJ, Green KG, Beyer EC, Saffitz JE. Effects of angiotensin II on expression of the gap junction channel protein connexin43 in neonatal rat ventricular myocytes. J Am Coll Cardiol. 1998 Sep;32(3):800-807.
73. De Mello WC, Cherry RC, Manivannann S. Electrophysiologic and morphologic abnormalities in the failing heart: effect of enalapril on the electrical properties. J Card Fail. 1997; 3: 53–61.
74. De Mello WC. Cell coupling and impulse propagation in the failing heart. J Cardiovasc Electrophysiol. 1999; 10: 1409–1420.
75. De Mello WC, Crespo MJ. Correlation between changes in morphology, electrical properties, and angiotensin-converting enzyme activity in the failing heart. Eur J Pharmacol. 1999; 378: 187–194.
76. Crackower MA, Sarao R, Oudit GY, Yagil C, Kozieradzki I, Scanga SE, Oliveira- dos-Santos AJ, da Costa J,Zhang L, Pei Y, Scholey J, Ferrario CM, Manoukian AS, Chappell MC, Backx PH, Yagil Y, Penninger JM:Angiotensin- converting enzyme 2 is an essential regulator of heart function. Nature 2002, 417:822-828.
77. Zisman LS, Keller RS, Weaver B, Lin Q, Speth R,Bristow MR, Canver CC. Increased angiotensin-(1-7)-forming activity in failing human heart ventricles:evidence for upregulation of the angiotensin-converting enzyme Homologue ACE2. Circulation. 2003;108:1707-1712.
78.Crackower MA, Sarao R, Oudit GY, Yagil C, Kozieradzki I, Scanga SE, Oliveira-Dos-Santos AJ, Da Costa J, Zhang L, Pei Y, Scholey J, Ferrario CM, Manoukian AS, Chappell MC, Backx PH, Yagil Y, Penninger JM. Angiotensin-converting enzyme 2 is an essential regulator of heart function. Nature. 2002; 417: 822–828.
79. Fiona J. Warner, Rebecca A. Lew, A. Ian Smith,Daniel W. Lambert, Nigel M. Hooper,and Anthony J.Turner: Angiotensin-converting Enzyme 2 (ACE2), But Not ACE, Is Preferentially Localized to the Apical Surface of Polarized Kidney Cells. THE JOURNAL OF BIOLOGICAL CHEMISTRY VOL. 2005(47);280; 39353-39362.
80. Zisman LS, Keller RS, Weaver B, Lin Q, Speth R, Bristow MR, Canver CC. Increased angiotensin-(1–7)-forming activity in failing human heart ventricles. Evidence for upregulation of the angiotensin-converting enzyme homologue ACE2. Circulation. 2003 Oct 7;108(14):1707-12.
81. Goulter A, Goddard MJ, Allen JC, Clark KL. ACE2 gene expression is up-regulated in the human failing heart. 2004 May 19;2-19.
82.Johnston CI Tissue angiotensin converting enzyme in cardiac and vascular hypertrophy, repair, and remodeling. Hypertension. 1994; 23: 258–268.
83. Ferrario CM, Trask AJ, Jessup JA. Advances in the biochemical and functional roles of angiotensin converting enzyme 2 and angiotensin-(1–7) in the regulation of cardiovascular function. Am J Physiol Heart Circ Physiol. 2005; 289: 2281–2290.
84. De Mello WC, Cherry RC, Manivannann S. Electrophysiologic and morphologic abnormalities in the failing heart: effect of enalapril on the electrical properties. J Card Fail. 1997; 3: 53–61.
85.Ferrario CM, Trask AJ, Jessup JA. Advances in biochemical and functional roles of angiotensin-converting enzyme 2 and angiotensin-(1-7) in regulation of cardiovascular function. Am J Physiol. 2005;289:2281–2290.
86. Iwata M, Cowling RT, Gurantz D, et al. Angiotensin-(1-7) binds to specific receptors on cardiac fibroblasts to initiate antifibrotic and antitrophic effects. Am J Physiol. 2005;289:2356–2363.
87.Tom B, de Vries R, Saxena PR, et al. Bradykinin potentiation by angiotensin-(1-7) and ACE inhibitors correlates with ACE C- and Ndomain blockade. Hypertension. 2001;38:95–99.
88.Ferreira AJ, Santos RA, and Almeida AP. Angiotensin-(1–7): cardioprotective effect in myocardial ischemia/reperfusion. Hypertension 2001;38: 665–668.
89. Ferreira AJ, Santos RA, and Almeida AP. Angiotensin-(1–7) improves the post-ischemic function in isolated perfused rat hearts. Braz J Med Biol Res 2002;35:1083–1090.
90. De Mello WC. Angiotensin (1–7) re-establishes impulse conduction in cardiac muscle during ischaemia-reperfusion. The role of the sodium pump. J Renin Angiotensin Aldosterone Syst 2004(5): 203–208.
91.Ferrario CM, Jessup J, Chappell MC, et al. Effect of angiotensin-converting enzyme inhibition and angiotensin II receptor blockers on cardiac angiotensin-converting enzyme 2. Circulation. 2005;111:2605–2610.
92.Seyedi N, Xu X, Nasjletti A, et al. Coronary kinin generation mediates nitric oxide release after angiotensin receptor stimulation. Hypertension. 1995;26:164–70.
93. Liu YH, Yang XP, Sharov VG, et al. Effects of angiotensin-converting enzyme inhibitors and angiotensin II type 1 receptor antagonists in rats with heart failure. Role of kinins and angiotensin II type 2 receptors. J Clin Invest. 1997;99:1926–35.
94.Jugdutt BI, Xu Y, Balghith M, et al. Cardioprotection induced by AT1R blockade after reperfused myocardial infarction: association with regional increase in AT2R, IP3R and PKC proteins and cGMP. J Cardiovasc Pharmacol Ther. 2000;5:301–311.
95. Xu Y, Menon V, Jugdutt BI. Cardioprotection after angiotensin II type 1 blockade involves angiotensin II type 2 receptor expression and activation of protein kinase C-epsilon in acutely reperfused myocardial infarction in the dog. Effect of UP269-6 and losartan on AT1 and AT2-receptor expression and IP3 receptor and PKCe proteins. J Renin Angiotensin Aldosterone Syst. 2000;1:184–195.
96. Jugdutt BI, Balghith M. Enhanced regional AT2-receptor and PKC expression during cardioprotection induced by AT1-receptor blockade after reperfused myocardial infarction. J Renin Angiotensin Aldosterone Syst. 2001;2:134–140.
97.Campbell DJ, Krum H, Esler MD. Losartan increases bradykinin levels in hypertensive humans. Circulation. 2005;111:315–20.
98. Ishiyama Y, Gallagher PE, Averill DB, Tallant EA, Brosnihan KB, and Ferrario CM. Upregulation of angiotensin-converting enzyme 2 after myocardial infarction by blockade of angiotensin II receptors. Hypertension 2004;43: 970–976.
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