Vascular remodeling and ET-1 expression in rat strains with different responses to chronic hypoxia

Chronic hypoxia leads to a greater degree of pulmonary hypertension in the Wistar-Kyoto (WKY) rat than in the Fischer 344 (F-344) rat. We questioned w hether this difference is associated with baseline differences in pulmonary artery anatomy, a greater degree of hypoxia-induced pulmonary vascular rem odeling in the WKY rat, and/or differences in expression of endothelin (ET) -1. Male F-344 and WKY rats were maintained in normoxia or normobaric hypox ia for 21 days. Morphometry revealed that baseline pulmonary artery anatomy was similar in the two strains. However, during chronic hypoxia, the WKY r ats developed a greater degree of muscularization of small pulmonary arteri es. Baseline plasma and lung immunoreactive ET-1 levels were similar in the WKY and F-344 rats and increased significantly during hypoxia in the WKY r ats. Northern analysis demonstrated increased lung preproET-1 mRNA during h ypoxia in both strains, with a greater increase in WKY rats. Immunostaining demonstrated increased ET-1 in bronchial epithelium and peripheral pulmona ry arteries dining hypoxia, although to a greater degree in the WKY rats. W e conclude that the WKY strain demonstrates increased susceptibility to hyp oxia-induced pulmonary vascular remodeling compared with the F-344 strain a nd that increased lung and circulating ET-1 levels during hypoxia may partl y explain this difference.