Effect of 12-hour infusions of saralasin or captopril on blood pressure in hypertensive conscious rats. Relationship to plasma renin, duration of hypertension, and effect of unclipping

Abstract

Saralasin (Sar1, Ala8 angiotensin II), a competitive antagonist of angiotensin II, or captopril, an angiotensin-converting enzyme inhibitor, were infused for 12 hr into conscious rats with Goldblatt two-kidney one-clip hypertension at an early stage (mean interval from clipping 36 days) and a chronic stage (151 days). In the early phase infusions of either saralasin or captopril produced a significant fall in blood pressure, which was maximal at 30 min, although the majority of animals remained hypertensive. In the chronic phase, saralasin produced a small and nonsignificant fall in blood pressure, whereas captopril produced a fall similar to that observed in the early group. No further fall in blood pressure was seen over the 12 hr period. PRC was markedly elevated in the early phase but did not differ significantly from normal in the chronic phase. The blood pressure fall produced by saralasin was significantly correlated with preinfusion PRC (r = 0.72 for the early group and 0.81 for the chronic group; p less than 0.01), whereas the fall in blood pressure produced by captopril was poorly correlated with PRC (r = 0.04 and 0.14, respectively). Captopril produced a minor fall and saralasin a minor elevation of blood 3 pressure in normal animals. Infusions of dextrose without inhibitor caused no change in blood pressure. Removal of the renal artery clip normalized blood pressure in the majority (88%) of animals in either the early or chronic phases. It is concluded that 12 hr infusions of these inhibitors are no more effective than 30 min infusions and do not fully correct hypertension in this model. Furthermore, the greater vasodepressor effect of captopril compared to saralasin in chronic hypertensive animals and the lack of correlation between PRC and change in blood pressure with captopril suggest that this agent has an action independent from blockade of the renin-angiotensin system. Removal of the renal artery clip is more effective than renin-angiotensin blockade in correcting Goldblatt two-kidney one-clip hypertension.