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RESEARCH PRODUCT

Potential of the EPA/DHA 6/1 formulation to prevent endothelial dysfunction and cardiopulmonary remodeling in pulmonary arterial hypertension in rats

subject

description

Pulmonary arterial hypertension (PAH) is characterized by remodeling of the small pulmonary arteries leading to a progressive increase in pulmonary vascular resistance and right ventricular failure. Pulmonary endothelial dysfunction, inflammation and oxidative stress promote the development of pulmonary hypertension. Omega-3 polyunsaturated fatty acids such as eicosapentaenoic acid (EPA) and docosahexaenoic acids (DHA) have been shown to protect the cardiovascular system and reduce inflammation and oxidative stress. The present study evaluate the potential of EPA:DHA 6:1 to prevent monocrotaline-induced PAH in rats. EPA:DHA 6:1 treatment (500 mg/kg/d, p.o) prevented the MCT-induced mean pulmonary arterial pressure, right ventricular systolic pressure and decreased cardiac output. EPA:DHA 6:1 also attenuated right ventricular hypertrophy by reducing Fulton’s index and pulmonary arterial remodeling, decreased lymphocytes T and macrophages infiltration. EPA:DHA 6:1 treatment significantly reduced MCT-induced vascular oxidative stress and improved endothelial function in pulmonary arteries. The protective effect of EPA:DHA 6:1 was associated with the prevention of the MCT-induced upregulation of NADPH oxidase subunits (p22phox and p47phox), COX-1 and COX-2, endothelin A and B receptors and uncoupled eNOS in pulmonary arterioles. Our studies show that the EPA:DHA 6:1 formulation exerts anti-inflammatory, anti-oxidant and has a protective vascular effect in the pulmonary arteries, which may contribute to prevent and potentially cure pulmonary hypertension induced by MCT in rat.