Combined renin and converting enzyme inhibition in rats

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)