Endothelin-3 effects on renal function and prostanoid release in the rat isolated kidney.
The direct effects of rat endothelin (ET-3) on renal function and prostanoid levels were examined in the isolated, oncotically perfused kidney of the rat. ET-3 at 0.75 and 2.0 ng/ml produced sustained increases in perfusion pressure of 46 and 83 mm Hg, respectively, as compared with control kidneys. Glomerular filtration rate was significantly higher than control after additions of ET-3 as was the absolute and fractional excretion of water and electrolytes. ET-3 increased perfusate 6-keto-prostaglandin (PG)F1 alpha (breakdown product of PGI2) levels and stimulated greater urinary excretion of PGE2 and PGF2 alpha than 6-keto-PGF1 alpha. ET-3 did not affect urinary excretion or perfusate levels of thromboxane B2. Time-dependent increases in renin release were suppressed by ET-3. Indomethacin (10 microM) prevented ET-3-induced increases in urinary and perfusate prostanoids; however, renal vasoconstrictor and excretory responses were the same in the presence or absence of indomethacin. These results indicate that ET-3 acts directly on the perfused rat kidney to increase the release of prostanoids from the vascular and urinary compartments. A modulatory influence of prostaglandins on the acute renal hemodynamic and excretory effects of ET-3 was not observed under these conditions.
Stier
C T
CT
Department of Pharmacology, New York Medical College, Valhalla.
Quilley
C P
CP
McGiff
J C
JC
D000818:Animals; D004573:Electrolytes / Q000652:urine; D016232:Endothelins / Q000494:pharmacology*; D005919:Glomerular Filtration Rate / Q000187:drug effects; D006439:Hemodynamics / Q000187:drug effects; D007213:Indomethacin / Q000494:pharmacology; D007668:Kidney / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D011453:Prostaglandins / Q000652:urine*; D051381:Rats; D011919:Rats, Inbred Strains
D004573:Electrolytes; D016232:Endothelins; D011453:Prostaglandins; D007213:Indomethacin