Effects of endothelin-1 and endothelin-3 on the release of prostanoids from isolated perfused rat kidney.
Endothelin-1 (ET-1) or endothelin-3 (ET-3) injected (0.1-100 pmol) into the renal artery of the isolated perfused rat kidney resulted in a dose-dependent increase in perfusion pressure (delta PP). In this respect, ET-1 was 30 times more potent than ET-3. Infusion of ET-1 (3 nM) for 3 min induced a pronounced and long-lasting rise in delta PP, in contrast to a transient increase in delta PP after a 3-min infusion of ET-3 (10 nM). The pressure effect of endothelins was associated with the appearance of 6-keto-PGF1 alpha and PGE2 but not TXB2 in the perfusate. ET-1 produced a transient release of comparable amounts of prostacyclin and PGE2. In contrast to ET-1, ET-3 evoked a sustained release of prostacyclin and PGE2 at a ratio 3:1. It is assumed that PGE2 contributed to the vasoconstrictor responses of the endothelins in the rat kidney because indomethacin (5.6 microM) attenuated the pressor responses induced by ET-1 to a larger extent than that induced by ET-3. These results are in line with earlier observations that PGE2 is a vasoconstrictor in rat kidney. The differential release of prostanoids by ET-1 and ET-3 suggests the existence of separate receptors for ET-1 and ET-3 in the rat kidney. ET-3 appears to be a good candidate for an endogenous regulator of the release of prostacyclin.
Trybulec
M
M
Department of Pharmacology, N. Copernicus Medical Academy, Cracow, Poland.
Dudek
R R
RR
Gryglewski
R J
RJ
D015121:6-Ketoprostaglandin F1 alpha / Q000378:metabolism; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D015232:Dinoprostone / Q000378:metabolism; D016232:Endothelins / Q000494:pharmacology*; D066298:In Vitro Techniques; D007668:Kidney / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D011453:Prostaglandins / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains; D014661:Vasoconstriction / Q000187:drug effects
D016232:Endothelins; D011453:Prostaglandins; D015121:6-Ketoprostaglandin F1 alpha; D015232:Dinoprostone