COMPARISON OF EFFECTS OF ANGIOTENSIN-CONVERTING ENZYME-INHIBITION WITH THOSE OF ANGIOTENSIN-II RECEPTOR ANTAGONISM ON FUNCTIONAL AND METABOLIC RECOVERY IN POSTISCHEMIC WORKING RAT-HEART AS STUDIED BY [P-31] NUCLEAR-MAGNETIC-RESONANCE

To assess the role of angiotensin II (AII) in development of myocardia l injury during ischemia and reperfusion, the effects of short-term tr eatment with the angiotensin-converting enzyme (ACE) inhibitor lisinop ril were compared with the effects of short-term treatment with L-158, 338, an AII antagonist, in isolated working rat heart. Myocardial func tion was assessed and correlated with simultaneous measurement of high -energy phosphate metabolism and intracellular pH by [P-31] nuclear ma gnetic resonance (NMR) before, during, and after global ischemia. Hear ts from rats treated with 1 mg/kg lisinopril in vivo recovered substan tially more function than those of controls (p < 0.001), whereas 50 ng /ml (0.11 mu M) lisinopril in vitro had no effect on functional recove ry. A dose-dependent increase in functional recovery was observed in r at heart treated with 0.3, 1, or 3 mg/kg L-158,338 in vivo (p < 0.005) . Treatment with 50 ng/ml (0.12 mu M) L-158,338 in vitro also resulted in increased functional recovery (p < 0.02). Significantly milder aci dosis during ischemia and significantly increased coronary flow were c haracteristic of the improved functional recovery exhibited by the gro ups treated with either lisinopril or L-158,338 in vivo. Treatment wit h L-158,338 in vitro caused significantly increased coronary flow duri ng reperfusion as compared with either its control group or with lisin opril treatment in vitro. High-energy phosphate metabolism was essenti ally unchanged by any treatment regimen. AII antagonism alone resulted in a degree of improvement in functional recovery comparable to that observed with oral ACE inhibitor treatment.