Angiotensin-converting enzyme inhibition with quinapril (CI-906) and captopril in spontaneously hypertensive rats with suppressed renin-angiotensin system

Renin- and nonrenin-mediated antihypertensive actions of angiotensin-converting enzyme (ACE) inhibitors were investigated in young spontaneously hypertensive rats (SHR). Renin was suppressed either by removal of 2/3 of the renal mass, deoxycorticosterone (DOC) treatment, or 1% of NaCl in drinking water. Blood pressure responses to the nonsulfhydryl ACE inhibitor quinapril (CI-906) and the sulfhydryl inhibitor captopril, given orally for 2 days each, were examined by the tail cuff method. The marked depressor responses observed in control SHR were attenuated by the different manipulations in a manner clearly related to suppression of plasma renin activity (PRA). The decrease in blood pressure falls and in PRA was smallest in partially nephrectomized SHR. The mineralocorticoid (DOC) administration or 1% NaCl reduced PRA and the responses to ACE inhibitors markedly, though not completely. In a further experiment, severe salt retention induced by DOC and NaCl in uninephrectomized SHR suppressed PRA to an unmeasurable level and prevented the depressor action of a large dose of captopril. The results suggest that in SHR the acute blood pressure-lowering effect of ACE inhibitors is completely dependent on the renin-angiotensin system. The experiments also show that this system clearly participates in the support of rapidly increasing blood pressure in young SHR.