Effects of angiotensin II AT(1)-receptor blockade on coronary dynamics, function, and structure in postischemic heart failure in rats

Angiotensin II AT(1)-receptor blockers (AT(1)(-)s) prolong survival in expe rimental postischemic (coronary artery ligation) heart failure (CHF) in rat s. The goal of this study was to investigate whether potential beneficial e ffects of short- and/or long-term treatment with AT(1)(-)s on coronary dyna mics, function, and structure develop along with the drug-induced survival prolongation in this model. Coronary blood flow was measured (fluorescent m icrospheres) in conscious sham, untreated, and irbesartan-treated (50 mg/kg daily for 6 weeks or 6 months, starting 8 days after surgery) CHF rats at baseline and at maximal vasodilatation induced by dipyridamole, and coronar y dilatation reserve (CDR) was calculated as the ratio of maximal to baseli ne coronary flow. Coronary endothelial function was assessed in vitro by me asuring the coronary relaxant responses to acetylcholine in the three group s of animals. Finally, cardiac hypertrophy and pericoronary fibrosis also w ere investigated. Tn CHF rats, left (LV) and right (RV) ventricular CDR wer e markedly depressed at both 7 weeks and 6 months after ligation, whereas c oronary endothelial function was significantly impaired only after 6 months . Short-term AT(1)-receptor blockade with irbesartan did not prevent CDR de terioration at 7 weeks, nor did it significantly oppose cardiac hypertrophy and pericoronary fibrosis development. Prolonged AT(1)-receptor blockade p revented both RV CDR deterioration and coronary endothelial function impair ment. It also limited significantly the increase in LV end diastolic pressu re and the development of cardiac hypertrophy and pericoronary fibrosis. In conclusion, in postischemic CHF in rats, alterations of CDR precede those of coronary endothelial function. Long-, but not short-term AT(1)-receptor blockade prevents endothelial function degradation, opposes RV CDR impairme nt, prevents pericoronary fibrosis development, and improves systemic hemod ynamics. These effects of AT(1)(-)s on coronary dynamics, function, and str ucture (i.e., on myocardial perfusion) may contribute to the drug-induced s urvival prolongation in this model.