0369 : The optimized omega-3 EPA:DHA 6:1 product prevents the monocrotaline-induced pulmonary arterial hypertension and vascular remodeling in rats

Abstract

Pulmonary arterial hypertension (PAH) is characterized by an increased pulmonary vascular resistance, right ventricular hypertrophy and increased systolic pressure. Omega-3 polyunsaturated fatty acids such as eicosapentaenoic acid (EPA) and docosahexaenoic acids (DHA) have been shown to protect the cardiovascular system and reduce inflammatory responses. We have investigated the cardiopulmonary protective effects of an optimized omega-3 fatty acid formulation (EPA:DHA 6:1) on the monocrotaline (MCT)-induced PAH in rats. Male Wistar rats received 500 mg/kg/day of either EPA:DHA 6:1 or corn oil by daily gavage. After one week, PAH was induced by a single subcutaneous injection of MCT (60 mg/kg). Three weeks following MCT, echocardiography was used to examine cardiac function, right ventricular (RV) systolic pressure, and pulmonary artery dimension. Endothelial function was assessed in pulmonary artery rings by vascular reactivity, right ventricular hypertrophy and pulmonary vascular morphometry by histology and immunohistochemistry, and oxidative stress using dihydroethidium. MCT induced pulmonary vascular remodeling, RV hypertrophy, endothelial dysfunction, and increased RV pressure and vascular ROS formation. Compared to the MCT group, EPA:DHA 6:1 treatment protected the pulmonary artery acceleration time, cardiac remodeling and prevented the elevation of right ventricular systolic pressure. Moreover, EPA:DHA 6:1 prevented the MCT-induced pulmonary artery endothelial dysfunction and increased wall thickness of pulmonary arterioles. This effect was associated with prevention of the MCT-induced upregulation of eNOS, AT1R, COX-2, COX-1 and the NADPH oxidase subunits (p22phox and p47phox). The present findings indicate that the optimized EPA:DHA 6:1 formulation has a cardioprotective effect in PAH, by preventing right ventricular failure and pulmonary arterial remodeling, endothelial dysfunction and oxidative stress. The author hereby declares no conflict of interest