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Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)

Effects of the endothelin ET(A) receptor antagonist, TA-0201, on pulmonary arteries isolated from hypoxic rats.

To investigate the roles of endothelin-1 in the pathogenesis of hypoxic pulmonary hypertension, we studied the effects of a selective endothelin ET(A) receptor antagonist, TA-0201 (N-(6-(2-(5-Bromopyrimidin-2-yloxy) ethoxy)-5-(4-methylphenyl) pyrimidin-4-yl)-4-(2-hydroxy-1,1-dimethylethyl) benzensulfonamide sodium salt sesquihydrate), on helical strips of pulmonary arteries isolated from hypoxia-induced pulmonary hypertensive rats as compared with those of normoxic rats. Endothelin-1-induced maximum contractions were significantly inhibited by exposure to hypoxia in the pulmonary arterial strips, but not in the mesenteric arterial strips. The hypoxia also induced right ventricular hypertrophy in rats. Addition of TA-0201 to the bath inhibited the endothelin-1-induced contraction of pulmonary arterial strips isolated from hypoxic rats more effectively than in those of normoxic rats. Oral administration of TA-0201 to hypoxic rats inhibited the hypoxia-induced right ventricular hypertrophy, and decreased the maximum contractile response to endothelin-1 in pulmonary arterial strips isolated from these rats. Those inhibitory effects induced by the oral administration of TA-0201 were not observed in the pulmonary arteries from normoxic rats or in the mesenteric arteries from both hypoxic and normoxic rats. These results suggest that endothelin-1 has important pathophysiological roles in hypoxia-induced pulmonary hypertension, and that TA-0201 may inhibit the endothelin-l-induced contraction through a change in the function of endothelin ET(A) receptor as well as competitive inhibition for endothelin ET(A) receptor.[1]


  1. Effects of the endothelin ET(A) receptor antagonist, TA-0201, on pulmonary arteries isolated from hypoxic rats. Itoh, H., Yokochi, A., Yamauchi-Kohno, R., Maruyama, K. Eur. J. Pharmacol. (1999) [Pubmed]
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