G. Matsuo et al., EFFECTS OF SARAFOTOXIN S6C ON RENAL HEMODYNAMICS AND URINE FORMATION IN ANESTHETIZED DOGS, Clinical and experimental pharmacology and physiology, 24(7), 1997, pp. 487-491
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.