RENAL ACTIONS OF ENDOTHELIN-1 AND ENDOTHELIN-3 - INTERACTIONS WITH THE PROSTAGLANDIN SYSTEM AND NITRIC-OXIDE

Endothelins (ET) possess both vasodilatory and vasoconstrictive proper ties. The renal actions of ET-1 and ET-3, as well as in vivo interacti ons of these two isopeptides with the prostaglandin and endothelium-de rived relaxation factor/nitric oxide systems were studied in anestheti zed dogs, The ETs were infused intrarenally at doses not affecting sys temic hemodynamics, Both ET-1 and ET-3 induced an early transient rena l vasodilation, followed by a prolonged vasoconstriction. Inhibition o f nitric oxide synthase with NC-monomethyl-L-arginine completely aboli shed the renal vasodilation induced by either ET-1 or ET-3 and enhance d the vasoconstriction. Endothelin-1 was associated with an increase i n the renal release of prostacyclin, while urinary thromboxane A, was increased after ET-3 administration, Inhibition of cyclooxygenase (wit h indomethacin) augmented the renal vasoconstriction induced by ET-1, but inhibition of cyclooxygenase (with meclofenamate) abolished the ET -3-evoked vasoconstriction, Endothelin-l showed little effects on urin ary water and sodium excretion; however, ET-3 displayed significant di uretic and natriuretic effects, which were inhibited by nitric oxide s ynthase inhibition, These findings suggest that these two isopeptides activate the endothelial endothelium-derived relaxation factor/nitric oxide system, which elicits early renal vasodilation, whereas direct e ffects on the vascular smooth muscle leads to vasoconstriction, Endoth elin-3 causes diuresis and natriuresis, possibly by inducing release o f nitric oxide in medullary collecting duct cells. (C) 1995 by the Nat ional Kidney Foundation, Inc.