Chronic administration of angiotensin-(1-7) attenuates pressure-overload left ventricular hypertrophy and fibrosis in rats

Abstract

Abstract: Background To test the hypothesis that chronic administration of angiotensin-(1-7) attenuates cardiac hypertrophy in rats in vivo.Methods Coarctation of the suprarenal abdominal aorta was performed in 41 8-week-old male Sprague Dawley rats. Twenty-four hours after the operation, osmotic minipumps were surgically implanted subcutaneously in the rats, which were randomly divided into 3 groups, including a sham-operation group (n=15) receiving infusion with normal saline, a suprarenal aortic coarctation group (n=12), and a suprarenal aortic coarctation group (n=14) with Ang-(1-7) treatment at the dose of 25 μg·kg^-1·h^-1. Four weeks later, the systolic and diastolic blood pressures were measured and the left ventricular mass index (LVMI, mg/g) was calculated from the ratio of left ventricular weight to body weight. The concentrations of Ang II in the plasma and myocardium were measured by radioimmunoassay, and myocardial interstitial collagen volume fraction (ICVF) was determined by quantitative morphometry of the sections with Picrosirius red staining using an automated image analyzer.Results Suprarenal abdominal aortic coarctation induced a significant increase in carotid artery systolic and diastolic blood pressure, heart weight, LVMI, ICVF, and the concentration of Ang II in the myocardium (P<0.01). Chronic administration of Ang-(1-7) attenuated the increase in the heart weight, LVMI, ICVF and left ventricular diastolic end pressure (LVEDP) caused by suprarenal abdominal aortic coarctation (P<0.05). Ang-(1-7) also increased the formerly decreased maximum left ventricular pressure reduction rate (-dP/dt_max) (P<0.05), but had no effect on blood pressure and the concentration of Ang II in the myocardium. No difference was noted in plasma concentration of Ang II between the 3 groups.Conclusions Ang-(1-7) attenuates cardiac hypertrophy and fibrosis and preserved the impaired left ventricular function induced by left ventricular pressure-overload in rats. These effects are not associated with the changes in the concentrations of Ang II in the left ventricular myocardium and plasma.

CLC Number:

R331

WANG Li-jun, HE Jian-gui, MA Hong, CAI Yi-ming, LIAO Xin-xue, ZENG Wu-tao, LIU Jun, WANG Li-chun. Chronic administration of angiotensin-(1-7) attenuates pressure-overload left ventricular hypertrophy and fibrosis in rats[J]. Journal of Southern Medical University, 2005, 25(05): 481-487.

References

[1] Brilla CG, Weber KT. Reactive and reparative myocardial fibrosis in arterial hypertension in the rat [J]. Cardiovasc Res, 1992, 26(7):671-7.
[2] Weber KT, Brilla CG. Pathological hypertrophy and cardiac interstitium: fibrosis and renin-angiotensin-aldosterone system [J].Circulation, 1991, 83(6):1849-65.
[3] Ikeda Y, Nakamura T, Takano H, et al. Angiotensin Ⅱ-induced cardiomyocyte hypertrophy and cardiac fibrosis in stroke-prone spontaneously hypertensive rats [J]. J Lab Clin Med, 2000, 135(4):353-9.
[4] Swynghedauw B. Molecular mechanisms of myocardial remodeling [J]. Physiol Rev, 1999, 79(1): 215-62.
[5] Iyer SN, Chappell MC, Averill DB, et al. Vasodepressor actions of angiotensin-(1-7) unmasked during combined treatment with lisinopril and losartan [J]. Hypertension, 1998, 31(2): 699-705.
[6] Santos RA, Campagnole-Santos MJ, Andrade SP. Angiotensin-(1-7):an update[J]. Regul Pept, 2000,91(1-3):54-62.
[7] Chappell M C, Tallant E A, Brosnihan KB, et al. Conversion of angiotensin I to angiotensin- (1-7) by thimet oliogopeptidase (E.C.3.4.24.15) in vascular smooth muscle cells [J]. J Vasc Biol Med,1995, 5(2): 129-37.
[8] Welches W R, Brosnihan K B, Ferrario CM. A comparison of the properties and enzymatic activities of three angiotensin processing enzymes: angiotensin converting enzyme, prolyl endopeptidase and neutral endopeptidase 24.11 [J]. Life Sci, 1993, 52(18): 1461-80.
[9] Vickers C, Hales P, Kaushik V, et al. Hydrolysis of biological peptides by human angiotensin-converting enzyme-related carboxypeptidase[J]. J Biol Chem, 2002, 277(17): 14838-43.
[10] Donoghue M, Hsieh F, Baronas E, et al. A novel angiotensinconverting enzyme-related carboxypeptidase (ACE2) converts angiotensin I to angiotensin 1-9[J]. Circ Res, 2000, 87(5): E1-9.
[11] Crackower MA, Sarao ROG, Yagil C, et al. Angiotensin-converting enzme 2 is an essential regulator of heart function [J]. Nature 2002,417(6891): 822-8.
[12] Chappell M C, Pirro N T, Sykes A, et al. Metabolism of angiotensin(1-7) by angiotensin-converting enzyme [J]. Hypertension, 1998, 31(1Pt 2): 362-7.
[13] Benter IF, Diz DI, Ferrario CM. Pressor and reflex sensitivity is altered in spontaneously hypertensive rats treated with angiotensin(1-7)[J]. Hypertension, 1995, 26 (6 Pt 2): 1138-44.
[14] Moriguchi A, Tallant EA, Matsumum K, et al. Opposing actions of angiotensin- (1-7) and angiotensin Ⅱ in the brain oftransgenic hypertensive rats[J]. Hypertension, 1995, 25(6): 1260-5.
[15] 曾武涛,马虹,鲁伟,等.血管紧张素-(1-7)在血管紧张素Ⅱ诱导心肌细胞肥大中的作用[J].中华心血管病杂志,2000,28(6):460-3.Zeng WT, Ma H, Lu W, et al. The role of angiotensin-(1-7) in myocardial cell hypertrophy induced by angiotensin Ⅱ [J]. Chin J Cardiol, 2000, 28(6): 460-3.
[16] 曾武涛,马虹,冷秀玉,等.血管紧张素-(1-7)对血管紧张素Ⅱ诱导心肌细胞原癌基因c-fos表达的影响[J].中国心血管杂志,2003,8(1):9-11.Zeng WT, Ma H, Leng XY, et al. Effects of angiotensin-(1-7) on the expression of proto-oncogene c-fos in cardiomyocyte induced by angiotensin Ⅱ[J]. Chin J Cardiovasc Med, 2003, 8(1): 9-11.
[17] Jouannot P, Hatt P. Rat myocardial mechanics during pressure-induced hypertrophy development and reversal[J]. Am J Physiol, 1975, 229(2): 355-64.
[18] Loot AE, Roks AJ, Henning RH, et al. Angiotensin-(1-7) attenuates the development of heart failure after myocardial infarction in rats [J]. Circulation, 2002, 105(13): 1548-50.
[19] Santos RA, Simoes e Silva AC, Maric C, et al. Angiotensin-(1-7) is an endogenous ligand for the G protein-coupled receptor Mas [J].Proc Natl Acad Sci U S A, 2003, 100(14): 8258-63.
[20] Takemoto M, Egashira K, Usui M, et al. Important role of tissue angiotensin-converting enzyme activity in the pathogenesis of coronary vascular and myocardial structural changes induced by long-term blockade of nitric oxide synthesis in rats [J]. J Clin Invest,1997, 99(2): 278-87.
[21] Frohlich ED. Risk mechanisms in hypertensive heart disease [J].Hypertension, 1999, 34(4):782-9.
[22] Weber KT. The what, why, and how of hypertensive heart disease [J]. J Hum Hypertens, 1994, 8(9): 665-75.
[23] Weber KT. Angiotensin Ⅱ and connective tissue: homeostasis and reciprocal regulation[J]. Regul Pept, 1999, 82(1-3): 1-17.
[24] Sun Y, Ratajska A, Zhou G, et al. Angiotensin converting enzyme and myocardial fibrosis in rats receiving angiotensin Ⅱ and aldosterone[J]. J Lab Clin Med 1993, 122(4): 395-403.
[25] Levy BI, Michel JB, Salzmann JL, et al. Effects of chronic inhibition of converting enzyme on mechanical and structural properties of arteries in rat renovascular hypertension[J]. Circ Res, 1988, 63(1):227-39.
[26] Linz W, Schaper J, Wiemer G, et al. Ramipril prevents left ventricular hypertrophy with myocardial fibrosis without blood pressure reduction: a one year study in rats[J]. Br J Pharmacol, 1992, 107(4): 970-5.
[27] Kobayashi S, Yano M, Kohno M, et al. Influence of aortic impedance on the development of pressure-overload left ventricular hypertrophy in rats[J]. Circulation, 1996, 94(12): 3362-8.
[28] Tokuda K, Kai H, Kuwahara F, et al. Pressure-independent effects of angiotensin Ⅱ on hypertensive myocardial fibrosis [J]. Hypertension,2004, 43(2): 499-503.
[29] Ren Y, Garvin JL, Carretero OA. Vasodilator action of angiotensin(1-7) on isolated rabbit afferent arterioles [J]. Hypertension, 2002,39(6): 799-802.
[30] Ferrario CM, Chappell MC. Novel angiotensin peptides [J]. Cell Mol Life Sci, 2004, 61(21): 2720-7.
[31] Luque M, Martin P, Martell N, et al. Effects of captopril related to increased levels ofprostacyclin and angiotensin- (1-7) in essential hypertension[J]. J Hypertens 1996, 14(6): 799-805.
[32] Machado RD, Ferreira MA, Belo AV, et al. Vasodilator effect of angiotensin-(1-7) in mature and sponge-induced neovasculature [J].Regul Pept, 2002, 107(1-3): 105-13.
[33] Machado RD, Santos RA, Andrade SP. Mechanisms of angiotensin(1-7)-induced inhibition of angiogenesis [J]. Am J Physiol(RICP),2001, 280(4): R994-R1000.
[34] 曾武涛,董吁钢,马虹,等.血管紧张素-(1-7)对血管紧张素Ⅱ诱导培养乳鼠非心肌细胞增殖的影响[J].中山医科大学学报,2001,22(4):241-4Zeng WT, Dong YG, Ma H, et al. The influence of Angiotensin-(1-7) on proliferation of cultured cardiac non-myocytes of neonatal rats induced by angiotensin Ⅱ [J]. Acad J SUMS, 2001, 22 (4):241-4.
[35] Mahon JM, Can RD, Nicol AK, et al. Angiotensin-(1-7) is an antagonist at the type 1 angiotensin Ⅱ receptor [J]. J Hypertens,1994, 12(12): 1377-81.
[36] Ueda S, Masumori-Maemoto S, Ashino K, et al. Angiotensin-(1-7)attenuates vasoconstriction evoked by angiotensin Ⅱ but not by noradrenaline in man [J]. Hypertension, 2000, 35(4): 998-1001.
[37] Roks AJM, van Geel PP, Pinto YM, et al. Angiotensin-(1-7) is a modulator of the human rennin-angiotensin system [J]. Hypertension,1999, 34(2): 296-301.
[38] Strewn WB, Ferrario CM, Tallant EA. Angiotensin-(1-7) reduces smooth muscle growth after vascular injury[J]. Hypertension, 1999,33(1 Pt 2): 207-11.
[39] Santos RA, Ferreira AJ, Nadu AP, et al. Expression of an angiotensin(1-7)-producing fusion protein produces cardioprotective effects in rats[J], Physiol Genomics, 2004, 17(3): 292-9.