Resveratrol (RVT) is a polyphenolic phytoalexin, and it has been demonstrated to be capable of protecting against cardiovascular disease. The aim of this study was to identify whether RVT might protect against monocrotaline (MCT)-induced pulmonary hypertension and whether vascular endothelial growth factor (VEGF), endothelial nitric oxide synthase (eNOS), and inducible nitric oxide synthase (iNOS) are involved in the beneficial effects.

Thirty Sprague Dawley rats were divided into three groups: the control (n=6), the MCT (n=12) and the MCT with RVT (5 mg/kg/day, n=12) groups. After 28 days, the tissue samples were obtained for morphometric analysis and Western blotting.

In the MCT group, the right ventricle/(left ventricle+septum) weight ratio was significantly increased compared with that of the control group (0.51±0.07 vs. 0.20±0.03, p<0.01), which was markedly suppressed in the RVT treated group (0.35±0.08, p<0.01). Histological analysis also showed that MCT treatment increased the medial wall thickness of the pulmonary arterioles compared with that of the control group (36±8% vs. 17±5%, p<0.01), which also was significantly suppressed in the RVT treated group (27±5%, p<0.01). In addition, Western blot demonstrated the decreased expression of VEGF in the MCT group (p<0.01), which was upregulated after long term RVT treatment (p<0.01). The expression of eNOS was increased after MCT treatment (p<0.01), but upregulation of eNOS could not be reversed by the RVT treatment. The expression of iNOS was not significantly modulated.

These results suggest that RVT attenuates MCT-induced pulmonary hypertension and it may represent a new strategy for the treatment of pulmonary hypertension.