The role of endothelin-1 in strain-related susceptibility to develop hypoxic pulmonary hypertension in rats

The Hilltop (H) strain compared to the Madison (M) strain of Sprague-Dawley rats develops severe pulmonary hypertension in response to chronic hypoxia . We tested the hypothesis that endothelin-1 (ET-1) contributes to these st rain-related differences. Plasma ET-1 content was not modified by chronic h ypoxia in either strain. The lung ET-1 peptide and preproET-1 mRNA content were significantly increased to the same magnitude in both strains at 2 and 3 weeks of hypoxia. The ETA receptor mRNA increased more at 3 weeks of hyp oxia in the lungs of H rats than in M rats. but not at other time points. T he ETB receptor mRNA was not modified by hypoxia in either strain. After 3 days of normoxic recovery following 2 weeks of hypoxia, ET-1 protein and mR NA levels decreased to baseline levels in both rat strains. We conclude tha t ET-1 does not contribute to the development of cardiopulmonary difference s between the H and M strains in response to hypoxia. (C) 2001 Elsevier Sci ence B.V. All rights reserved.