Effects of chronic converting enzyme inhibition on the vascular renin-angiotensin system

1. The effects of chronic oral administration of inhibitors of angiotensin converting enzyme (ACE) on the vascular renin-angiotensin system were studied. 2. Male Sprague-Dawley rats were treated orally with five ACE inhibitors, captopril, enalapril, ramipril, cilazapril and CS-622 (10 mg/kg per day), for periods of 1-2 weeks. Their mesenteric arteries were then isolated and perfused in vitro with Krebs'-Ringer solution, and the angiotensin II (AII) released into the perfusate was measured under unstimulated and isoproterenol-stimulated conditions. The vascular renin activity was also determined after treatments with ACE inhibitors. 3. Treatment with captopril for 1 week suppressed the isoproterenol-stimulated increase in AII release, but had little effect on the baseline release. Oral treatment with captopril for 2 weeks or with other ACE inhibitors for 1 week markedly inhibited both the unstimulated and stimulated release of AII from the mesenteric vasculature. 4. Both the vascular renin activity and the plasma renin activity increased on captopril treatment, but their changes with time were different. 5. These results indicate that virtually complete inhibition of the vascular renin-angiotensin system can be achieved after prolonged treatment with ACE inhibitors, and suggest that the chronic antihypertensive action of ACE inhibitors is not solely due to inhibition of the plasma renin-angiotensin system.