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 [31P] Nuclear Magnetic Resonance

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Abstract
To assess the role of angiotensin II (AII) in development of myocardial injury during ischemia and reperfusion, the effects of short-term treatment with the angiotensin-converting enzyme (ACE) inhibitor lisinopril were compared with the effects of short-term treatment with L-158,338, an AII antagonist, in isolated working rat heart. Myocardial function was assessed and correlated with simultaneous measurement of high-energy phosphate metabolism and intracellular pH by [31P] nuclear magnetic resonance (NMR) before, during, and after global ischemia. Hearts from rats treated with 1 mg/kg lisinopril in vivo recovered substantially more function than those of controls (p < 0.001), whereas 50 ng/ml (0.11 microM) lisinopril in vitro had no effect on functional recovery. A dose-dependent increase in functional recovery was observed in rat 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 microM) L-158,338 in vitro also resulted in increased functional recovery (p < 0.02). Significantly milder acidosis during ischemia and significantly increased coronary flow were characteristic of the improved functional recovery exhibited by the groups treated with either lisinopril or L-158,338 in vivo. Treatment with L-158,338 in vitro caused significantly increased coronary flow during reperfusion as compared with either its control group or with lisinopril treatment in vitro. High-energy phosphate metabolism was essentially 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.

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