Clofibrate improves myocardial ischemia-induced damage through regulation of renin-angiotensin system and favours a pro-vasodilator profile in left ventricle

摘要: Abstract Myocardial ischemia initiates a chain of pathological conditions leading to cardiomyocyte death. Therefore, pharmacological treatment stop ischemia-induced damage is necessary. Fibrates, have been reported decrease inflammatory markers and modulate the renin-angiotensin system (RAS). Our aim was explore if clofibrate treatment, administered one week after myocardial event, decreases MI-induced cardiac damage. Wistar rats were assigned to: 1. Sham or 2. Coronary artery ligation (MI). Seven days after, subdivided receive vehicle (V) [100 mg/kg (C)] daily for 7 days. Blood samples left ventricle analyzed. RAS components [angiotensin II, angiotensin converting enzyme (ACE), AT1-receptor] decreased in MI-C compared MI-V, while [Ang-(1–7), bradykinin, ACE-2, AT2-receptor] raised response treatment. Oxidative stress increased MI-V rats, profile reverted rats. Nitric oxide (NO) pathway (Akt, eNOS, NO) exhibits lower participation but NO-pathway its production. fibrosis structural also improved by clofibrate-treatment. In conclusion, administration MI-rats exerts an antioxidant, pro-vasodilator expression profile, anti-fibrotic effect suggesting that PPARα activation can be considered therapeutic target improve condition posterior ischemia.