Oral sildenafil prevents and reverses the development of pulmonary hypertension in monocrotaline-treated rats.
The endothelin system plays an important 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.
Department of Cardiothoracic Surgery, Zhongda Hospital, Southeast University, Nanjing 210009, China.
Hao
H
Liu
Zhi-yong
ZY
Liu
Qin
Q
Guan
D000284:Administration, Oral; D000818:Animals; D000959:Antihypertensive Agents / Q000008:administration & dosage*; D001794:Blood Pressure / Q000187:drug effects; D004195:Disease Models, Animal; D019332:Endothelin-1 / Q000097:blood; D006976:Hypertension, Pulmonary / Q000139:chemically induced / Q000150:complications / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology / Q000517:prevention & control*; D017380:Hypertrophy, Right Ventricular / Q000209:etiology / Q000517:prevention & control; D008168:Lung / Q000098:blood supply / Q000187:drug effects / Q000473:pathology; D017563:Lung Diseases, Interstitial / Q000209:etiology / Q000517:prevention & control; D008297:Male; D016686:Monocrotaline; D010879:Piperazines / Q000008:administration & dosage*; D011651:Pulmonary Artery / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D011656:Pulmonary Emphysema / Q000209:etiology / Q000517:prevention & control; D011687:Purines / Q000008:administration & dosage; D051381:Rats; D017207:Rats, Sprague-Dawley; D044022:Receptor, Endothelin A / Q000378:metabolism; D000068677:Sildenafil Citrate; D013450:Sulfones / Q000008:administration & dosage*; D013997:Time Factors; D014665:Vasodilator Agents / Q000008:administration & dosage*
D000959:Antihypertensive Agents; D019332:Endothelin-1; D010879:Piperazines; D011687:Purines; D044022:Receptor, Endothelin A; D013450:Sulfones; D014665:Vasodilator Agents; D016686:Monocrotaline; D000068677:Sildenafil Citrate