Control of arterial pressure and renal function during chronic renin inhibition

Abstract

The aim of this study was to determine whether the renin inhibitor CP-71362 (Pfizer Central Research, Groton, Connecticut, USA) is capable of inducing sustained reductions in arterial pressure in sodium-depleted dogs and to examine the changes in renal function associated with chronic renin inhibition. In addition, we also examined the chronic effects on renal function and blood pressure of the angiotensin converting enzyme (ACE) inhibitor enalaprilat. Infusion of CP-71362 (1.1 micrograms/kg per min, intravenously) for 7 days decreased mean arterial pressure from 87 +/- 3 to 75 +/- 2 mmHg, while causing no significant changes in sodium excretion, the glomerular filtration rate, or effective renal plasma flow. Plasma renin activity was suppressed to undetectable levels throughout the 7 days of CP-71362 infusion. Infusion of enalaprilat (4 mg/kg per day) for 7 days in sodium-depleted dogs decreased mean arterial pressure (from 85 +/- 2 to 64 +/- 3 mmHg) and renal vascular resistance, and increased effective renal plasma flow and sodium excretion, but caused no significant changes in the glomerular filtration rate. Thus CP-71362 is a potent inhibitor of dog plasma renin, and we observed no waning of this inhibitory effect of CP-71362's hypotensive actions over 7 days. The mechanisms responsible for the differences in the blood pressure and renal responses to CP-71362 and ACE inhibition are not clear, but may be dose-related or due to differences in the distribution of these compounds to various tissues, including the kidney.