Prolongation of the saralasin responsive state of two-kidney, one clip Goldblatt hypertension in the rat by the orally administered converting enzyme inhibitor captopril (SQ14,225).

Two-kidney, one clip Goldblatt rats were treated with oral converting enzyme inhibitor captopril (SQ14,225) 6 mg/kg/day for 3 weeks after they had developed hypertension. Before treatment, systolic blood pressure rose from 143 to 202 mm Hg (p less than 0.05). Tail vein infusions of saralasin 10 microgram/kg/min in conscious rats reduced systolic blood pressure from 202 to 121 mm Hg (p less than 0.05) at 8 weeks after clipping the renal artery and before treatment with captopril. Chronic treatment with captopril for 3 additional weeks lowered blood pressure to 173 mm Hg (p less than 0.05). When saralasin infusion was repeated during treatment with captopril, blood pressure fell from 173 to 159 mm Hg (p less than 0.05). Blood pressure rose to 197 mm Hg within 4 days after captopril was discontinued and saralasin infusion 3 weeks after captopril (15 weeks after clipping the renal artery) again resulted in a dramatic fall in blood pressure from 197 to 142 mm Hg (p less than 0.05). Goldblatt rats who had not received captopril showed no blood pressure response to saralasin infusion at 12 weeks after renal artery clipping. The present study demonstrates that partial inhibition of the renin-angiotensin system with captopril results in a delay in the natural evolution of clip hypertension retarding the appearance of hypertension that is resistant to acute saralasin infusion.