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Oral sildenafil prevents and reverses the development of pulmonary hypertension in monocrotaline-treated rats

Department of Cardiothoracic Surgery, Zhongda Hospital, Southeast University, Nanjing 210009, China

*Corresponding author. Tel.: +86-25-83272003; fax: +86-25-83272011.

E-mail address: zyliu3{at}jsmail.com.cn (Z-y. Liu).

The endothelin system plays an importment role in the development of pulmonary hypertension. Several studies have suggested that interfering with the function of the endothelin system will be helpful in pulmonary hypertension treatment. In the present study, we investigated the preventive and therapeutic effects of sildenafil on pulmonary hypertension in monocrotaline-treated rats. In the preventive study, the level of mean pulmonary arterial pressure, right ventricular divide, left ventricular and septum, small pulmonary arterial morphologic and elastic fiber changes were highly improved in the treated group (P<0.05). The expressions of endothelin-1 A type receptors on small pulmonary arterial hypertension were significantly reduced in the sildenafil-treated group (P<0.05). The ET-1 level in plasma was increased in the sildenafil-treated group, but did not reach significance. Emphysema, interstitial pneumonia were significantly improved in the sildenafil-treated group. The same findings were also observed in the therapeutic study. The present results suggest that sildenafil can prevent and reverse the development of pulmonary hypertension in monocrotaline-treated rats by improving the function of endothelin system in pulmonary arteries.

Key Words: Endothelium; Experimental surgery; Myocardial remodeling; Pulmonary arteries; Vascular tone and reactivity

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