Haemodynamic influence and endothelin-1 plasma concentrations by selectiveor non-selective endothelin receptor antagonists in the pig in vivo

In the present study the haemodynamical effects of endothelin (ET)-receptor antagonism was evaluated using selective and non-selective ETA- and ETB-re ceptor blockade in normoxic pigs in vivo. In addition, the influence of the ET-antagonists on circulating plasma ET-1 levels was determined. BMS-18287 4 (10 and 30 mg kg(-1) i.v.), a selective ETA-receptor antagonist decreased the pulmonary and systemic vascular resistances, bosentan (10 and 30 mg(-1 ) i.v.), a non-selective ETA- and ETB-receptor antagonist caused principall y similar effects as ETA-antagonism alone. No effects were observed by sele ctive ETB-blockade using BQ-788 (30 mu g kg(-1) i.v.). Of the three antagon ists used only bosentan increased the circulating plasma ET-1 levels. It ma y therefore be concluded that ET contributes to basal systemic and pulmonar y vascular tone through ETA-receptor activation. ETB-receptors are likely t o cause the elevated plasma levels of ET-1 observed after bosentan administ ration. Furthermore, circulating plasma levels of ET-1 do not reflect the p hysiological effects of ET-1.