MODULATION BY ENDOGENOUS PROSTANOIDS OF THE VASOCONSTRICTOR ACTIVITY OF ENDOTHELIN-1 IN THE CANINE ISOLATED, PERFUSED SPLEEN

1 Endothelin-1 (ET-1, 0.4-200 pmol) was injected into the arterial cir cuit of the isolated perfused spleen of the dog in which splenic arter ial perfusion pressure and spleen weight were recorded continuously. 2 Serial collection was made of splenic venous effluent before and afte r intra-arterial injection of ET-1 and assayed by direct radioimmunoas say for prostaglandin E(2) (PGE(2)), 6-oxo-PGF(1 alpha) and thromboxan e B-2 (TXB(2)). 3 ET-1 caused graded arterial vasoconstriction of prol onged duration with small reductions in spleen weight at higher doses. 4 ET-1 cause a dose-related release of PGE(2), 6-oxo-PGF(1 alpha) and TXB(2) into the splenic venous effluent. The mean peak increase above the basal levels following 200 pmol of ET-1 was 800% for PGE(2), 233% for 6-oxo-PGF(1 alpha) and 205% for TXB(2). 5 Intra-arterial infusion of indomethacin significantly reduced the basal release of all three eicosanoids and significantly elevated the basal splenic vascular resi stance. The release of all three eicosanoids in response to ET-1 and a drenaline (Ad) was significantly reduced by indomethacin and the accom panying increases in the splenic arterial vascular resistance were sig nificantly potentiated at low doses of ET-1. The splenic arterial vasc ular responses to Ad were unchanged by indomethacin infusion. 6 These results indicate that the release of eicosanoids may modulate the sple nic vascular responses to ET-1.