Objective: To investigate whether valsartan ameliorated monocrotaline (MCT)-induced right ventricular-pulmonary arterial (PA) uncoupling in rats and its possible mechanisms. Methods: Ninety Sprague-Dawley rats were divided randomly into control, MCT+vehicle, and MCT+valsartan groups. Right ventricle (RV) hemodynamic parameters were determined by echocardiography and invasive right ventricular cannulation. The morphological changes of RV and pulmonary arterioles were assessed. The interstitial

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... brosis of RV myocardium and pulmonary was analyzed with Masson's trichrome staining. And RV myocardial apoptosis was detected by TUNEL assay. The protein expression of Fas, Bax, Bcl-2 and caspase-3 in RV myocardium was analyzed by Western Blotting. Results: RV-PA uncoupling, pulmonary vascular remodeling, RV hypertrophy, and interstitial fibrosis of lung and RV developed 3 wks after MCT administration. Alternatively, MCT induced RV apoptosis, associated with the upregulation of Fas, Bax, and caspase-3 expression, while downregulation of Bcl-2 expression. And these manifestations were significantly reversed by valsartan treatment. Conclusion: Valsartan can ameliorate RV-PA uncoupling, at least in part, by improving pulmonary arterioles and RV remodeling, and reducing collagen deposition, as well as lessening RV apoptosis via regulating the expression of Fas, caspase-3, Bcl-2 and Bax molecules in RV myocardium.