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Renal and systemic hemodynamics were studied in rats 1 month after induction of myocardial infarction by ligation of the left coronary artery. The mean arterial pressure, heart rate, and cardiac index were not different from controls, but there were striking elevations in heart weight (p < 0.001), left ventricular end diastolic pressure (p < 0.002), and renal vascular resistance (p < 0.01). Renal blood flow and the percent of cardiac output perfusing the kidneys were reduced by 18% (p < 0.01) and 14% (p < 0.01), respectively. Acute angiotensin inhibition was studied at a dose of the converting enzyme inhibitor, enalapril, or the renin inhibitor, CP71362, that lowered the mean arterial pressure by 15 mm Hg in normal rats. In normal rats, enalapril and CP71362 were without effect on renal blood flow (RBF), renal vascular resistance (RR), and RBF as a percent of cardiac output. However, in rats with myocardial infarction, enalapril and CP71362 increased the RBF and RBF as a percent of cardiac output and lowered the RR to levels similar to normal controls (p < 0.02). Enalapril and CP71362 were equally effective in reducing the left ventricular end-diastolic pressure and total peripheral resistance in rats with myocardial infarction. These data demonstrate significant intrarenal vasoconstriction following myocardial infarction in the absence of detectable changes in mean arterial pressure or cardiac index. Converting enzyme inhibition or renin inhibition had similar beneficial effects on cardiorenal function, suggesting that both classes of compounds act by a similar mechanism to improve renal hemodynamics in congestive heart failure.

The effects of combined renin inhibition and converting enzyme inhibition on mean arterial pressure and the plasma renin-angiotensin system were studied in conscious rats. In sodium-replete rats the infusion of the renin inhibitor CP71362 (100 micrograms/kg/min) decreased blood pressure by 13 +/- 1 mm Hg (p less than 0.0001), reduced plasma renin activity to undetectable levels, but did not lower plasma angiotensin II. In rats treated chronically with enalapril (30 mg/kg/day), CP71362 decreased blood pressure by an additional 5 +/- 2 mm Hg (p less than 0.025) and reduced plasma renin activity and angiotensin II concentrations to undetectable levels. The effects of renin inhibition were also tested under conditions where the renin-angiotensin system was stimulated. In rats on a low sodium diet, CP71362 decreased blood pressure by 15 +/- 2 mm Hg (p less than 0.0001), a decrease similar to that in rats on a normal diet. Plasma renin activity was decreased below detectable limits, but plasma angiotensin II concentrations were not reduced. In rats on a low sodium diet treated chronically with enalapril, CP71362 did not further decrease blood pressure although angiotensin II levels were significantly reduced. An additive effect of combined converting enzyme and renin inhibition on blood pressure lowering and inhibition of plasma angiotensin II was found in rats anesthetized with Inactin.(ABSTRACT TRUNCATED AT 250 WORDS)