Antidiuretic action of vasoactive endothelins in the in situ perfused rainbow trout kidney.

The present studies examined, for the first time, the renal actions of endothelin-1 (ET-1) and Sarafotoxin S6b (SRTX-6b) (an endothelin-like peptide from snake venom) at 10^-11 M and 10^-9 M, using the in situ perfused kidney of the rainbow trout, Oncorhynchus mykiss. In further studies ET-1 (10^-9 M) was accompanied by Captopril (5 × 10^-4 M) to inhibit angiotensin II formation and determine whether the newly-identified intrarenal renin-angiotensin system (RAS) in the trout kidney was involved in ET-1's actions. These studies demonstrated that ET-1 and SRTX-S6b constrict the trout trunk vasculature, increasing vascular resistance and decreasing perfusate flow rates. Captopril did not affect this response and therefore angiotensin II is not implicated in the vascular responses. Direct action of endothelins on vascular receptors is indicated which, in vivo, is likely to be involved in regulation of renal vascular tone. Both ET-1 and SRTX-6b induced immediate decreases in glomerular filtration rates (GFR) reaching 30% and 34% decrease with 10^-11 M ET-1 and SRTX-6b respectively and 50% and 57% decrease with 10^-9 M ET-1 and SRTX-6b respectively. Urine flow rates decreased to a slightly lesser extent because of decreased tubular reabsorption of water; relative free water clearances increased from approximately 17% to 21% while urine/plasma inulin concentration ratios decreased slightly. This significant depressed urine osmolarity. Captopril completely blocked the effects of endothelins on tubular water reabsorption suggesting intrarenal RAS involvement in this action, although a kinin-mediated effect cannot, at this stage, be excluded. The glomerular antidiuretic action of ET-1 and SRTX-6b partially reflected a decreased population of filtering nephrons (41% filtering in control kidneys, 32–36% filtering in the presence of 10^-11 M M ET-1/SRTX-6b, 31–32% filtering in the presence of 10^-9 M ET-1/SRTX-6b). In addition, 25–40% reductions of single nephron filtration rates were estimated. Glomerular actions of endothelins were partially inhibited by Captopril, suggesting either that renal endothelins have both direct renal actions and secondary effects through activation of the renal RAS, or that kinins can modulate the renal actions of endothelins. [ABSTRACT FROM AUTHOR]