Renal actions of endothelin-1 and endothelin-3: interactions with the prostaglandin system and nitric oxide.
Endothelins (ET) possess both vasodilatory and vasoconstrictive properties. The renal actions of ET-1 and ET-3, as well as in vivo interactions of these two isopeptides with the prostaglandin and endothelium-derived relaxation factor/nitric oxide systems were studied in anesthetized dogs. The ETs were infused intrarenally at doses not affecting systemic hemodynamics. Both ET-1 and ET-3 induced an early transient renal vasodilation, followed by a prolonged vasoconstriction. Inhibition of nitric oxide synthase with NG-monomethyl-L-arginine completely abolished the renal vasodilation induced by either ET-1 or ET-3 and enhanced the vasoconstriction. Endothelin-1 was associated with an increase in the renal release of prostacyclin, while urinary thromboxane A2 was increased after ET-3 administration. Inhibition of cyclooxygenase (with indomethacin) augmented the renal vasoconstriction induced by ET-1, but inhibition of cyclooxygenase (with meclofenamate) abolished the ET-3-evoked vasoconstriction. Endothelin-1 showed little effects on urinary water and sodium excretion; however, ET-3 displayed significant diuretic and natriuretic effects, which were inhibited by nitric oxide synthase 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 effects on the vascular smooth muscle leads to vasoconstriction. Endothelin-3 causes diuresis and natriuresis, possibly by inducing release of nitric oxide in medullary collecting duct cells.
Chou
S Y
SY
Division of Hypertension and Nephrology, Brookdale Hospital Medical Center, Brooklyn, NY 11212, USA.
Porush
J G
JG
D000594:Amino Acid Oxidoreductases / Q000037:antagonists & inhibitors; D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives / Q000494:pharmacology; D004231:Diuresis / Q000187:drug effects; D004285:Dogs; D016232:Endothelins / Q000494:pharmacology*; D011464:Epoprostenol / Q000378:metabolism; D007213:Indomethacin / Q000494:pharmacology; D007668:Kidney / Q000187:drug effects* / Q000378:metabolism / Q000502:physiology; D008469:Meclofenamic Acid / Q000494:pharmacology; D009318:Natriuresis / Q000187:drug effects; D009569:Nitric Oxide / Q000378:metabolism*; D019001:Nitric Oxide Synthase; D011453:Prostaglandins / Q000378:metabolism*; D012079:Renal Circulation / Q000187:drug effects; D013928:Thromboxane A2 / Q000652:urine; D014661:Vasoconstriction / Q000187:drug effects; D014664:Vasodilation / Q000187:drug effects; D019323:omega-N-Methylarginine
D016232:Endothelins; D011453:Prostaglandins; D019323:omega-N-Methylarginine; D009569:Nitric Oxide; D008469:Meclofenamic Acid; D013928:Thromboxane A2; D001120:Arginine; D011464:Epoprostenol; D019001:Nitric Oxide Synthase; D000594:Amino Acid Oxidoreductases; D007213:Indomethacin