Resveratrol Prevents Monocrotaline‐induced Pulmonary Hypertension in Rats

Progression of pulmonary hypertension (PAH) is associated with increased proliferation of pulmonary arterial smooth muscle cells (PASMCs) and activation of inflammatory processes. We showed previously that resveratrol (RES) in vitro exerts anti‐oxidant anti‐inflammatory effects and attenuates cell proliferation. The present study was undertaken to investigate the efficacy of RES for preventing PAH. Rats injected with monocrotaline (MCT) progressively developed PAH. RES treatment (25 mg/kg/day, p.o., from day 1 post‐MCT) attenuated RV systolic pressure and pulmonary arterial remodeling, decreased expression of inflammatory cytokines (TNFa, IL‐1a, IL‐6, PDGFa/b) and limited the presence of ED‐1 positive cells in the lung. RES in vitro inhibited proliferation of PASMCs. There was an increased expression of eNOS, decreased oxidative stress, down‐regulation of NAD(P)H oxidase subunits and improved endothelial function in small pulmonary arteries of RES‐treated rats. RES treatment also prevented RV hypertrophy and attenuated RV myocardial oxidative stress. In conclusion, RES exerts anti‐inflammatory and anti‐oxidant effects attenuating vascular remodeling and cor pulmonale in experimental PAH.