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  • Title: Haemodynamic influence and endothelin-1 plasma concentrations by selective or non-selective endothelin receptor antagonists in the pig in vivo.
    Author: Holm P, Franco-Cereceda A.
    Journal: Acta Physiol Scand; 1999 Feb; 165(2):163-8. PubMed ID: 10090327.
    Abstract:
    In the present study the haemodynamical effects of endothelin (ET)-receptor antagonism was evaluated using selective and non-selective ET(A)- and ET(B)-receptor blockade in normoxic pigs in vivo. In addition, the influence of the ET-antagonists on circulating plasma ET-1 levels was determined. BMS-182874 (10 and 30 mg kg(-1) i.v.), a selective ET(A)-receptor antagonist decreased the pulmonary and systemic vascular resistances. bosentan (10 and 30 mg(-1) i.v.), a non-selective ET(A)- and ET(B)-receptor antagonist caused principally similar effects as ETA-antagonism alone. No effects were observed by selective ET(B)-blockade using BQ-788 (30 microg kg(-1) i.v.). Of the three antagonists used only bosentan increased the circulating plasma ET-1 levels. It may therefore be concluded that ET contributes to basal systemic and pulmonary vascular tone through ET(A)-receptor activation. ET(B)-receptors are likely to cause the elevated plasma levels of ET-1 observed after bosentan administration. Furthermore, circulating plasma levels of ET-1 do not reflect the physiological effects of ET-1.
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