Endothelin-1 releases eicosanoids from rabbit isolated perfused kidney and spleen.
This study analyzes the effects of porcine endothelin-1 (ET-1) on perfusion pressure and eicosanoid release from rabbit isolated spleen and kidney. Bolus injections (2.5-50 pmol) or infusions (1, 5, and 10 nM) of ET-1 into either organ caused dose-related increases of perfusion pressure. Pressor responses were potentiated following infusion of indomethacin (5.6 microM) for 30 min. ET-1 triggered the release of cyclo-oxygenase products as revealed by bioassay and radioimmunoassay (RIA) analysis of the effluent. In the spleen, ET-1 stimulated the release of PGE2 mainly and, to a lesser extent, of PGI2 and TXA2. In the kidney, ET-1 stimulated a greater release of PGI2 than PGE2, but not TXA2. These results demonstrate that in the isolated rabbit spleen and kidney, ET-1 is a potent vasoconstrictor and triggers the generation of vasodilator eicosanoids that limit the pressor effects of the peptide.
Rae
G A
GA
William Harvey Research Institute, St. Bartholomew's Hospital Medical College, London, England.
Trybulec
M
M
de Nucci
G
G
Vane
J R
JR
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D015232:Dinoprostone / Q000494:pharmacology; D004537:Eicosanoic Acids / Q000378:metabolism*; D016232:Endothelins; D011464:Epoprostenol / Q000494:pharmacology; D066298:In Vitro Techniques; D007213:Indomethacin / Q000494:pharmacology; D007668:Kidney / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D010455:Peptides / Q000494:pharmacology*; D010477:Perfusion; D011817:Rabbits; D013154:Spleen / Q000187:drug effects / Q000378:metabolism*; D013928:Thromboxane A2 / Q000378:metabolism
D004537:Eicosanoic Acids; D016232:Endothelins; D010455:Peptides; D013928:Thromboxane A2; D011464:Epoprostenol; D015232:Dinoprostone; D007213:Indomethacin