Comparative effects of angiotensin converting enzyme inhibition (perindopril) or diuretic therapy on cardiac hypertrophy and sympathetic activity following myocardial infarction in rats

Abstract

The long-term effects of perindopril or chlorothiazide therapy were studied in rats after the induction of myocardial infarction by coronary artery ligation. Rats with infarction developed marked cardiomegaly, indicating the presence of chronic left ventricular dysfunction. The ratio of the norepinephrine metabolite, 3,4-dihydroxyphenylethylene glycol (DHPG) to norepinephrine (NE) was elevated in the right ventricle of rats with infarction, suggesting a chronic increase in cardiac sympathetic activity. Perindopril therapy commenced either immediately following infarction or 4 weeks following infarction reduced DHPG/NE ratios toward normal levels, and prevented or reversed cardiac hypertrophy. In contrast, chlorothiazide therapy significantly reduced DHPG/NE ratios but did not decrease cardiac hypertrophy. Perindopril reverses or prevents cardiac hypertrophy and chronic cardiac sympathetic hyperactivity following myocardial infarction, while chlorothiazide reduces cardiac sympathetic activity without influencing cardiomegaly.

Effect of a selective aldosterone receptor antagonist in myocardial infarction

“…Future studies directly addressing this hypothesis and its underlying mechanisms are warranted. These data are unlikely to be the result of a diuretic effect, because other much more potent diuretics fail to demonstrate protective effects in this model on characteristics of remodeling (14,18). In addition, a role for aldosterone in fibrosis and remodeling is especially significant given that the rat MI model is not characterized by chronic activation of RAAS, which suggests that normal plasma aldosterone levels are sufficient to support a role in post-MI remodeling.…”

Beneficial effects of add‐on hydrochlorothiazide in rats with myocardial infarction optimally treated with quinapril

“…Renin itself is not known to have direct cellular effects during post‐infarct cardiac remodelling. However, HCTZ alone decreases sympathetic activation in rats with MI [7]. Thus, the decrease in plasma renin is likely to be an indicator for improved therapy outcome rather than a mediator of HCTZ effects.…”

“…For heart failure treatment, this has not been investigated. Sodium depletion itself has never been shown to affect the progression of LV dysfunction in terms of LV remodelling [6 b9] or LV hemodynamic parameters [10]. However, induction of a negative sodium balance may provide a strategy to enhance the therapeutic efficacy of ACEi in heart failure.…”

Perindopril

“…10, N o . 4 , 1992 treatment (72,73,102,141). There was also a partial, but significant, prevention of the shift in the isomyosin profile (102).…”

“…Furthermore, in the noninfarcted part of the myocardium, in which electrophysiological changes are observed, perindopril normalized the duration of the repolarization phase of the action potential (141). This improvement of cardiac electrogenesis may be linked to a reduction of cardiac sympathetic hyperreactivity normally associated with coronary artery ligation (72,73,124). This could also explain the improvement of contractile function seen with perindopril in the same model (34).…”