O40 The omega-3 EPA:DHA 6:1 formulation prevents the monocrotaline-induced pulmonary hypertension, pulmonary artery remodelling, endothelial dysfunction, and right ventricular failure in rats

Abstract

Introduction Omega-3 polyunsaturated fatty acids such as eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) have been shown to protect the cardiovascular system and reduce inflammation. The possibility that the superior omega-3 formulation, EPA:DHA 6:1, prevents cardiopulmonary dysfunction and remodelling was evaluated in an experimental model of pulmonary arterial hypertension (PAH). Methods: Male Wistar rats received 500 mg/kg/day of either EPA:DHA 6:1 or corn oil by daily gavage for 4 weeks before sacrifice. After one week, PAH was induced by a single subcutaneous injection of monocrotaline (MCT, 60 mg/kg). Results MCT treatment was associated with increased systolic pulmonary arterial pressure (PAP) and blunted endothelium-dependent relaxations to acetylcholine in pulmonary artery rings, increased wall thickness and oxidative stress in pulmonary arterioles, and increased right ventricle (RV) systolic pressure and hypertrophy, and reduced cardiac output. The EPA:DHA 6:1 treatment prevented the MCT-induced changes in morphology and pressure in the pulmonary artery and RV. EPA:DHA 6:1 treatment also reduced the MCT-induced pulmonary artery endothelial dysfunction, and the level of oxidative stress in pulmonary arterioles. The protective effect of EPA:DHA 6:1 was associated with the prevention of the MCT-induced upregulation of eNOS, AT1 receptors, endothelin receptors, COX-1 and COX-2, and NADPH oxidase subunits in pulmonary arterioles, and reduced perivascular macrophage and lymphocyte infiltration in lungs. Conclusion The present findings indicate that the EPA:DHA 6:1 has a cardioprotective effect in PAH by preventing right ventricular failure, pulmonary artery and arterioles remodelling and endothelial dysfunction, most likely by preventing vascular oxidative stress.