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.