Effects of endothelin-3 on renal functions.
The effects of L-NGnitroarginine (LNNA), a nitric oxide synthase inhibitor, and ibuprofen, a cyclooxygenase inhibitor, on the renal actions induced by endothelin (ET)-3 were studied in anesthetized dogs. Continuous infusion of ET-3 in a dose of 5 ng/kg/min for 25 min increased both renal blood flow (RBF) and urine flow rate. In dogs given LNNA (75 micrograms/kg/min for 25 min), the RBF decreased after intrarenal administration of ET-3 (5 ng/kg/min). Glomerular filtration rate (GFR) was unchanged throughout the infusion of ET-3, in dogs treated with and without LNNA. In dogs given ibuprofen (12.5 mg/kg i.v.), an initial increase in RBF was evident after initiating infusion of the peptide, to be followed by a gradual reduction in RBF, GFR decreased significantly with ET-3, whereas the degree of reduction in RBF was the same in dogs treated with LNNA. Thus, ET-3 acts as a vasodilatory and diuretic peptide in the dog kidney. Presumably ET-3 enhances the release of nitric oxide and prostaglandins and then renal vasodilation occurs. Although the enhanced production of prostaglandins by ET-3 may be responsible for maintaining GFR, it is not linked to the initial phase of renal vasodilation.
Yamashita
Y
Y
Department of Pharmacology, Osaka City University Medical School, Japan.
Yukimura
T
T
Miura
K
K
Okumura
M
M
Yamamoto
K
K
D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives / Q000494:pharmacology; D004285:Dogs; D016232:Endothelins / Q000494:pharmacology*; D005260:Female; D007052:Ibuprofen / Q000494:pharmacology; D007668:Kidney / Q000098:blood supply / Q000187:drug effects / Q000502:physiology*; D008297:Male; D019335:Nitroarginine; D009599:Nitroprusside / Q000494:pharmacology; D012077:Renal Artery / Q000187:drug effects; D012079:Renal Circulation / Q000187:drug effects; D014563:Urodynamics / Q000187:drug effects; D014665:Vasodilator Agents / Q000494:pharmacology
D016232:Endothelins; D014665:Vasodilator Agents; D009599:Nitroprusside; D019335:Nitroarginine; D001120:Arginine; D000109:Acetylcholine; D007052:Ibuprofen