Increased rat cardiac angiotensin converting enzyme activity and mRNA expression in pressure overload left ventricular hypertrophy. Effects on coronary resistance, contractility, and relaxation.

Abstract

We compared the activity and physiologic effects of cardiac angiotensin converting enzyme (ACE) using isovolumic hearts from male Wistar rats with left ventricular hypertrophy due to chronic experimental aortic stenosis and from control rats. In response to the infusion of 3.5 X 10-8 M angiotensin I in the isolated buffer perfused beating hearts, the intracardiac fractional conversion to angiotensin II was higher in the hypertrophied hearts compared with the controls (17.3±4.1% vs 6.8±1.3%, P < 0.01). ACE activity was also significantly increased in the free wall, septum, and apex of the hypertrophied left ventricle, whereas ACE activity from the nonhypertrophied right ventricle of the aortic stenosis rats was not different from that of the control rats. Northern blot analyses of poly(A)+ purified RNA demonstrated the expression of ACE mRNA, which was increased fourfold in left ventricular tissue obtained from the hearts with left ventricular hypertrophy compared with the controls. In both groups, the intracardiac conversion of angiotensin I to angiotensin II caused a comparable dose-dependent increase in coronary resistance. In the control hearts, angiotensin II activation had no significant effect on systolic or diastolic function; however, it was associated with a dose-dependent depression of left ventricular diastolic relaxation in the hypertrophied hearts. These novel observations suggest that cardiac ACE is induced in hearts with left ventricular hypertrophy, and that the resultant intracardiac activation of angiotensin II may have differential effects on myocardial relaxation in hypertrophied hearts relative to controls. (J. Clin.

Antihypertensive treatment modulates the association between the D/I ACE gene polymorphism and left ventricular hypertrophy: a meta-analysis

“…First, there is mounting evidence that increased ACE gene expression and ACE activity may stimulate the local rate of angiotensin II production [46][47][48][49] and, in turn, may promote cardiac growth. Second, the D variant of the ACE gene may act only under specific conditions, when physiologic or pathophysiologic processes stimulate left ventricular enlargement.…”

Rodent models of heart failure: an updated review

“…1. For instance, in weanling rats [70,263,309,316], a TAC surgery that reduces 50% of the aorta diameter creates a systolic pressure gradient of *50-60 mmHg between the aorta and the LV, inducing clear echocardiographic evidence of LV hypertrophy, and increases left atrial pressure around the 8th week [162]. After 18-20 weeks of compensated LV hypertrophy, a subgroup of animals eventually decreases LV systolic pressure, accompanied by increased LV volume, reduced ejection fraction and clinical signs of overt CHF [309].…”

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

“…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].…”

“…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]. It has been reported that angiotensinogen and ACE mRNAs are increased in experimental left ventricular hypertrophy induced by hemodynamic overload [4]. ACE inhibitors with subpressor doses induced significant regression of cardiac hypertrophy with no change in systemic systolic blood pressure [1].…”