Renin-angiotensin system involvement in pressure-overload cardiac hypertrophy in rats

Abstract

We have recently shown that the octapeptide angiotensin II is a potent stimulus of protein synthesis and growth in cultured cardiomyocytes. The present study was performed to determine if the renin-angiotensin system was involved in regulating cardiac cell growth in vivo. The pressure-overload cardiac hypertrophy model that develops in abdominal aorta-constricted rats was studied. At 7 and 15 days after abdominal aorta constriction, rats developed significant left ventricular hypertrophy. The increase in left ventricular mass was completely prevented in animals fed the angiotensin-converting enzyme inhibitor, enalapril maleate (0.2 mg/ml) in their drinking water. Cardiac afterload was the same in both groups of animals in that carotid artery pressures were not different in conscious awake aortic-constricted animals receiving and not receiving enalapril. These data suggest a direct growth effect of angiotensin II on the left ventricle and indicate a role for the renin-angiotensin system in the cardiac hypertrophy that develops in response to pressure overload. The presence and chamber localization of angiotensinogen mRNA was determined using Northern hybridization and S1 nuclease mapping analysis. Angiotensinogen mRNA, as determined by dot-blot hybridization analysis, was significantly increased in hypertrophied left ventricles at both 7 and 15 days after the surgery, when compared with sham-operated controls. The activity of the circulating renin-angiotensin system, as indexed by plasma renin activity was increased at 1 day following surgery [6.0 +/- 2.0 ng.ml-1.h-1 angiotensin I (control) vs. 41.8 +/- 10.9 ng.ml-1.h-1 angiotensin I (experimental)], but returned to control values by day 3 postoperatively.(ABSTRACT TRUNCATED AT 250 WORDS)

Activation of p70 S6 protein kinase is necessary for angiotensin II‐induced hypertrophy in neonatal rat cardiac myocytes

“…A growing body of data has suggested that renin-angiotensin system plays an important role in generating cardiac hypertrophy [1][2][3][4][5][6][7]. In the present study, to elucidate the mechanism of the Ang II-induced cardiac hypertrophy, we examined the role of p70 s6K in cultured cardiac myocytes of neonatal rats.…”

“…Many lines of evidence have suggested that angiotensin II (Ang II) plays a critical role in inducing cardiac hypertrophy [1][2][3][4][5][6][7]. All components of the renin angiotensin system such as renin, angiotensinogen and angiotensin-converting enzyme (ACE) have been identified in the heart at both mRNA and protein levels [5,6].…”

Role of tissue angiotensin II in myocardial remodelling induced by mechanical stress

“…Moreover, an increase in LV mass produced by abdominal aortic constriction can be completely prevented by an ACE inhibitor without changes in afterload and plasma renin activity. 13 We further investigated the relation between hypertensive cardiac hypertrophy and the cardiac reninangiotensin system. 14 In an in vivo study, spontaneously hypertensive rats (SHR) were assigned to the treatment with a nonpeptide Ang II type 1 receptor antagonist of candesartan or a vasodilating agent of hydralazine.…”

ACE inhibition in aortic stenosis: dangerous medicine or golden opportunity?

“…7 Increased expression of both cardiac renin mRNA and cardiac angiotensinogen mRNA are seen under conditions of experimental chronic pressure overload in rats. 8,9 Expression of the ACE has also been demonstrated to be upregulated within the myocardium of rats with pressure overload induced LVH. [8][9][10][11] These findings suggest that increased expression of ACE in the presence of increased local production of renin and angiotensinogen produce increases in angiotensin II, as a response to pressure overload or damage, in the left ventricle.…”

“…8,9 Expression of the ACE has also been demonstrated to be upregulated within the myocardium of rats with pressure overload induced LVH. [8][9][10][11] These findings suggest that increased expression of ACE in the presence of increased local production of renin and angiotensinogen produce increases in angiotensin II, as a response to pressure overload or damage, in the left ventricle. 12,13 This activation of the cardiac renin-angiotensin system occurs independently of systemic angiotensin II generation.…”