INCREASED ENDOTHELIN RECEPTOR GENE-EXPRESSION IN HYPOXIC RAT LUNG

Our previous studies demonstrated that exposure to hypoxia increases p ulmonary artery pressure and plasma endothelin-1 (ET-1) levels and sel ectively enhances ET-1 gene expression in rat lung. The current study examined the effects of hypoxia (48 h, 10% O-2, 1 atm) on ET-1 and end othelin A (ET(A)) and ET(B) receptor steady-state mRNA levels in lung, heart, pulmonary artery, thoracic aorta, superior vena cava, kidney, spleen, and liver of the rat, In lung, hypoxic exposure was associated with significant increases in ET-1 mRNA (4.1-fold), ET-1 peptide (1.5 -fold) and ET(A) mRNA (2.3-fold) levels; ET(B) mRNA levels were unchan ged. ET-1 mRNA was increased in response to hypoxia in pulmonary arter y but not in aorta; both ET(A) and ET(B) receptor steady-state mRNA le vels were increased in thoracic aorta, left atrium, and right ventricl e, and tended to be increased in right atrium of hypoxia-exposed rats, compared with air controls. ET(B) but not ET(A) receptor steady-state mRNA levels were increased in pulmonary artery of hypoxia-exposed rat s. No change in expression of either ET receptor steady-state mRNA lev els was seen in organs perfused by the systemic vascular bed. In no ca se were ET receptor mRNA levels in hypoxic rats reduced below air cont rol levels, despite elevations in local and/or circulating ET-1. These findings are consistent with a role for ET-1, acting through ET(A) re ceptors, in the pathogenesis of hypoxia-induced pulmonary hypertension .