The Molecular Mechanism Of Resveratrol In Prevention And Treatment Of Pulmonary Arterial Hypertension

Background:Pulmonary Arterial Hypertension is an increased cause of mortality in modern society with multifactorial pathobiology, like proliferation of smooth muscle cells, and leukocyte infiltration. Resveratrol (RES), a potent anti-free radical and anti-inflammations, has been demonstrated possessing a direct vessel relaxation property. This study will evaluate the effect of RES treatment in PAH and tested the hypothesis that the anti-oxidant, anti-inflammatory, and anti-proliferation properties of RES prevent or reverse the process of PAH. The statistical analysis was conducted using the Statistical Package for Social Science 17.0 (SPSS Inc, IL). All data are given as the mean±SEM. Analysis of variance between two groups was determined by one-way ANOVA test. P< 0.05 was accepted as statistically significant.Methods:Rats (n=36) injected with 50 mg/kg of MCT subcutaneously 4 weeks to develop PAH were then randomized to either RES (5 mg/kg per day) or placebo group for another 4 weeks. Hemodynamics was evaluated via direct measurement. The structural remodeling and inflammation of the pulmonary vessels were examined by histologic and ectromicrospic observation. The effects of RES on expression and activity of iNOS and cyclic guanosine monophosphate (cGMP)-dependent protein kinase 1(PKG-1) were detected by Immunohistochemical staining and Western Blot. The generation of ROS and anti-oxidation species was measured by Biochemical Analyses.Results:MCT increased PAH and RV hypertrophy. And RES treatment alleviated pulmonary Arterial pressure elevation (20.88±1.53 vs 11.22±0.57, P<0.05), right ventricular hypertrophy (57.69±4.46vs31.672±1.33, P<0.05), leukocyte infiltration, and structural remodeling of pulmonary Arterial induced by MCT successful (95.33vs77.75, P<0.01). Also RES treatment significantly increased expression of PKG-1 and suppressed expression of iNOS. The activity of Superoxide Dismutase (SOD), glutathione peroxidase (GSH) and catalase (CAT) activities were significantly higher than control group while level of MDA was lower in RES group.Conclusion:RES can suppress established PAH induced by MCT. The underlying mechanisms may be associated With its ability of anti-inflammatory, antioxidant, inhibiting the expression of iNOS, increased PKG-1 expression, resveratrol prevent pulmonary damage hypertrophy and vascular diastolic, this is a new mechanism for RES in prevention and treatment of pulmonary arterial hypertension.