Effects of continuous converting enzyme blockade on renovascular hypertension in the rat

Abstract

The effects of continuous converting enzyme blockade throughout the early angiotensin-dependent phase on the subsequent development of chronic 1-kidney hypertension in the rat was studied. Continuous blockade of angiotensin II formation was also studied in the 2-kidney rat. Converting enzyme blockade was achieved for 1 day before and for 12 days after renal artery constriction; the converting enzyme inhibitor SQ 14,225 [2-D-methyl-3-mercaptopropanoyl-L-proline] was infused at 80 and 160 .mu.g/h via minipumps placed in the abdomen. In both the 1 and 2 kidney hypertensive control groups (no drug), a significant elevation in systolic blood pressure was observed by the 4th day after clipping and systolic pressures were maintained at hypertensive levels thereafter. SQ 14,225 (80 .mu.g/h) prevented a significant rise in systolic blood pressure in 2-kidney rats for 12 days after renal artery clipping; 2 days after administration of SQ 14,225 was stopped (14 days after clipping) systolic pressure increased and subsequently achieved hypertensive levels. Infusion of SQ 14,225 into 1-kidney rats (80 and 160 .mu.g/h) prevented a significant rise in systolic pressure until the 8th day after clipping, but systolic pressure then increased to hypertensive levels despite continuous converting enzyme blockade for an additional 4 days. The renin-angiotensin system plays an essential role in the pathogenesis of 2-kidney hypertension in the rat. An acute increase in the activity of the renin-angiotensin system is unnecessary to trigger a primary pathogenic mechanism for chronic 1-kidney hypertension in the rat.