Study of the indomethacin and bradykinin antagonism in anaesthetized dogs

To determine the prostaglandin dependent and independent effects of bradykinin in the kidney, bradykinin (0.05 microgram/min/kg body weight) was infused into the left renal artery during inhibition of prostaglandin synthesis by indomethacin. Indomethacin, 0.1 mg/min/kg body weight i.v. produced a marked fall in urine output and sodium excretion in anaesthetized dogs. Renal vascular resistance increased and renal blood flow (RBFdir) decreased by 30%. When during the i.v. infusion of indomethacin bradykinin was infused into the left renal artery, RBFdir, urine flow and sodium excretion increased to the control values in the left kidney while remained lower in the right kidney. The results suggest that bradykinin increases renal blood flow by an action which does not require the mediation of prostaglandins. A decrease in renal blood flow, which was a constant feature during i.v. indomethacin infusion, is probably responsible for the decrease in urine flow and sodium excretion. The failure of indomethacin to inhibit the natriuretic and diuretic effects of bradykinin suggests that the prostaglandins are not important determinants of these responses.