EFFECT OF AN ANGIOTENSIN-II AND A KININ RECEPTOR ANTAGONIST ON THE RENAL HEMODYNAMIC-RESPONSE TO CAPTOPRIL

The role of angiotensin II and kinins on the renal cortical and papillary hemodynamic and on the sodium and water excretory responses to converting enzyme inhibition with captopril was examined in euvolemic Munich-Wistar rats. Cortical and papillary blood flows were measured using a laser Doppler flowmeter. Cortical blood flow increased 28% after blockade of angiotensin II receptors with DuP 753 (2 mg/kg i.v., n = 6). Captopril (2 mg/kg i.v., n = 6) had no effect on cortical blood flow in rats pretreated with the angiotensin II antagonist. DuP 753 had no effect on papillary blood flow, nor did it prevent the rise in papillary blood flow produced by captopril (2 mg/kg, n = 6). Infusion of a kinin receptor antagonist, D-Arg,[Hyp3,Thi5,8, D-Phe7]-bradykinin (2.5-mu-g/min i.v.), reduced basal papillary blood flow by 15% and blocked the rise in papillary blood flow produced by captopril. Renal blood flow rose by 11% after DuP 753 (2 mg/kg, n = 6), and subsequent administration of captopril and the kinin antagonist had no effect on renal blood flow. Urine flow and sodium excretion increased after DuP 753, but captopril produced additional increases in urine flow and sodium excretion of 68% and 46%, respectively. Fractional sodium excretion rose from 0.85 +/- 0.15% to 15% to 1.56 +/- 0.14% after captopril. Infusion of the kinin antagonist returned sodium and water excretion to control levels, but fractional sodium excretion was not significantly altered. Glomerular filtration rate was not altered by DuP 753 or captopril; however, it fell from 1.6 +/- 0.1 to 1.2 +/- 0.1 ml/min/g kidney wt during infusion of the kinin antagonist. This fall in glomerular filtration rate was associated with a 30% fall in the ultrafiltration coefficient. These results indicate that captopril alters renal hemodynamics through mechanisms other than blockade of the renin-angiotensin system. In particular, its effects on papillary blood flow and glomerular dynamics may be due to alterations in the intrarenal levels of kinins.