Resveratrol prevents pulmonary trunk remodeling but not right ventricular hypertrophy in monocrotaline-induced pulmonary hypertension

Pulmonary hypertension (PAH) is characterized by abnormal vascular remodeling and increased pulmonary artery pressure which lead to right ventricular (RV) hypertrophy and heart failure. Resveratrol (3,5,4′-trihydroxy-trans-stilbene), a dietary polyphenol found in the skins and seeds of grapes, has been found to have antioxidant, anti-proliferative and anti-fibrotic effects. This study examined the effects of resveratrol on cardiac and pulmonary trunk remodeling, and common plasma markers of vascular function in rats with PAH was induced in male Sprague-Dawley rats by a single subcutaneous injection of monocrotaline (MCT, 60mg/kg). Rats were treated with resveratrol (25mg/kg/day) by oral gavage daily for 21days. PAH was confirmed by the presence of increased RV/LV+septum weight, RV and lung weight. In MCT rats, total heart surface area and RV lumen area were increased without corresponding increases in total muscle area, indicating a dilation of the lumen. Pulmonary truck lumen area and thickness of the tunica media were increased by 43% and 44%, respectively, by MCT. Resveratrol had no significant effect on remodeling, although decreases of 12% and 27% were observed for overall heart area and pulmonary truck area, respectively. However, resveratrol significantly reduced the thickness of the pulmonary trunk tunica media. Plasma levels of angiotensin II, aldosterone, C-reactive protein and endothelin-1 were not altered with resveratrol. Our results indicate that daily treatment with resveratrol does not inhibit the abnormal remodeling of the RV induced by MCT, but attenuates the development of medial hypertrophy in the pulmonary trunk.