ANTIDIURETIC ACTION OF VASOACTIVE ENDOTHELINS IN THE IN-SITU PERFUSEDRAINBOW-TROUT KIDNEY

The present studies examined, for the first time, the renal actions of endothelin-l (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 sit u perfused kidney of the rainbow trout, Oncorhynchus mykiss. In furthe r studies ET-1 (10(-9) M) was accompanied by Captopril (5 x 10(-4) M) to inhibit angiotensin II formation and determine whether the newly-id entified intrarenal renin-angiotensin system (RAS) in the trout kidney was involved in ET-l's actions. These studies demonstrated that ET-1 and SRTX-S6b constrict the trout trunk vasculature, increasing vascula r resistance and decreasing perfusate flow rates. Captopril did not af fect this response and therefore angiotensin II is not implicated in t he vascular responses. Direct action of endothelins on vascular recept ors is indicated which, in vivo, is likely to be involved in regulatio n of renal vascular tone. Both ET-1 and SRTX-6b induced immediate decr eases in glomerular filtration rates (GFR) reaching 30% and 34% decrea se with 10(-11) M ET-1 and SRTX-6b respectively and 50% and 57% decrea se with 10(-9) M ET-1 and SRTX-6b respectively. Urine flow rates decre ased to a slightly lesser extent because of decreased tubular reabsorp tion of water; relative free water clearances increased from approxima tely 17% to 21% while urine/plasma inulin concentration ratios decreas ed slightly. This significant depressed urine osmolarity. Captopril co mpletely blocked the effects of endothelins on tubular water reabsorpt ion suggesting intrarenal RAS involvement in this action, although a k inin-mediated effect cannot, at this stage, be excluded. The glomerula r antidiuretic action of ET-I and SRTX-6b partially reflected a decrea sed population of filtering nephrons (41% filtering in control kidneys , 32-36% filtering in the presence of 10(-11) M ET-1/SRTX-6b, 31-32% f iltering in the presence of 10(-9) M ET-1/SRTX-6b). In addition, 25-40 % reductions of single nephron filtration rates were estimated. Glomer ular actions of endothelins were partially inhibited by Captopril, sug gesting either that renal endothelins have both direct renal actions a nd secondary effects through activation of the renal RAS, or that kini ns can modulate the renal actions of endothelins.