Role of extrarenal and intrarenal converting enzyme inhibition in renal vasodilator response to intravenous captopril

Participation of intrarenal converting enzyme (ICE) in mediation of the renal vasodilator response to captopril (C) was studied in 7 anesthetized dogs. Blood pressure (BP), renal blood flow (RBF) and femoral blood flow (FBF) were measured and vasoconstrictor responses were elicited by i.a. injections of angiotensin (A) I to the renal and femoral vascular beds. The latter responses served as indices of intrarenal and skeletal muscle converting enzyme activity, respectively. Successive infusions of C were given i.a. to the kidney at 0.4, 0.8 and 1.6 μg/kg/min for 30 min each. RBF and renal vascular resistance (RVR) were unaffected by any of these doses of C. The % changes in RBF caused by A-I were reduced from 45 to 23, 20 and 17% by these successive doses of C, respectively; however, the decrements were not significantly different from each other. When C was administered i.v., 0.5 mg/kg, after the highest i.a. dose had been given, there was no further decrease in the response to A-I, suggesting maximal blockade of ICE obtainable by C. BP, RBF and RVR were further affected by the i.v. administration of C. BP decreased from 146 to 136 mm Hg (P<0.05), RBF increased from 240 to 290 ml/min (P<0.01) and RVR decreased from 32 to 24 mm Hg/ml/min/g (P<0.01). These results suggest that ICE plays a minor role in the renal vasodilator response to C, and implicate an influence of circulating peptides on the kidney.