EFFECTS OF SARAFOTOXIN S6C ON RENAL HEMODYNAMICS AND URINE FORMATION IN ANESTHETIZED DOGS

1. The effects of sarafotoxin S6c (S6c), a selective endothelin ETB re ceptor agonist, on renal haemodynamics and urine formation were examin ed in anaesthetized dogs. 2. Intrarenal arterial infusion of S6c at a rate of 1 or 5 ng/kg per min produced a transient increase in renal bl ood flow (RBF), with no change in systemic blood pressure and heart ra te; RBF then decreased gradually to below the basal value, There were significant and dose-dependent increases in urine flow and free water clearance and decreases in urine osmolality during S6c infusion, where as urinary excretion of sodium and glomerular filtration rate (GFR) re mained unchanged. Simultaneously, S6c administration elicited a marked increase in urinary excretion of nitric oxide (NO) metabolites, NO2- and NO3- (UNOxV). 3. In dogs simultaneously administered S6c (5 ng/kg per min) and N-G-nitro-L-arginine (NOARG; 40 mu g/kg per min), a NO sy nthase inhibitor, the renal vasodilator effect of S6c was abolished an d marked reductions in RBF and GFR were observed. The S6c-induced diur etic action was not affected by NOARG. In the presence of NOARG, there was a small amount of UNOxV at the basal level and the administration of S6c did not increase UNOxV. 4. These results suggest that an intra renal arterial infusion of S6c enhances the production of NO in the ki dney and that this enhancement contributes to the peptide-induced rena l vasodilation. In contrast, it is unlikely that S6c-induced water diu resis is related to NO production stimulated by this peptide.