Peroxisome proliferator-activated receptor-α stimulation by clofibrate favors an antioxidant and vasodilator environment in a stressed left ventricle

Abstract Background Arterial high blood pressure is a risk factor for target organ damage; the most susceptible organs are the arteries, brain, kidneys, and heart. The damage mechanisms include oxidative stress and renin-angiotensin system (RAS) overactivity. Therefore, our aim was to study whether clofibrate-induced peroxisome proliferator-activated receptor-alpha (PPAR-α) stimulation is able to prevent alterations in cardiac functioning derived from RAS overstimulation in the left ventricle of rats with hypertension secondary to aortic coarctation and to improve antioxidant defenses. Methods Male Wistar rats were assigned to Control (Sham)- or aortic coarctation-surgery and further divided to receive (1 or 21 days) vehicle, clofibrate (100 mg/kg), captopril (20 mg/kg), or clofibrate + captopril. The left ventricle was obtained to measure: angiotensin II and -(1–7), AT 1 and AT 2 receptors, angiotensin converting enzyme (ACE)-1 and -2, and MAS receptor; the activity and expression of superoxide dismutase, catalase, endothelial nitric oxide synthase, the production of reactive oxygen species (ROS) and peroxidated lipids; as well as ex vivo cardiac functioning. Results Clofibrate decreased angiotensin II, AT 1 receptor and ACE expression, and raised angiotensin-(1–7), AT 2 receptor, ACE-2 expression, superoxide dismutase and endothelial nitric oxide synthase participation. These effects promoted lower coronary vascular resistance and improved mechanical work compared to aortic coarctated vehicle-treated rats. Conclusions Clofibrate-induced PPAR-α stimulation changes the angiotensin II receptor profile, favors the ACE2/angiotensin-(1–7)/AT 2 receptor axis decreasing the vasoconstrictor environment, activates the antioxidant defense, and facilitates endothelial nitric oxide synthase activity favoring vasodilation. This may represent a protection for the stressed heart.