Cardioprotective role of myocardial endothelial nitric oxide synthase and serum nitric oxide induced by hexarelin in rats with myocardial infarction-induced heart failure

Abstract

Background: Growth hormone-releasing peptides (GHRP) have been reported to possess cardioprotective properties; nonetheless, their mechanisms of action are still not very clear. Objectives: Some studies have suggested that modulation of endothelial nitric oxide synthase (eNOS) and the upregulation of nitric oxide (NO) are cardioprotective. Therefore, the present study strived to test the hypothesis that a potent GHRP analog (hexarelin) could increase serum nitric oxide level and regulate myocardial eNOS to alleviate the development of heart failure. Methods: Myocardial infarction-induced heart failure in rats was established by permanent coronary artery ligation. The sham group, control group, and heart failure group all received normal saline (100 µg/kg; SC BID; 30days), while the rats in the hexarelin treatment group were treated with hexarelin (100 µg/kg, SC BID, 30 days). The rats were tested for myocardial apoptosis, oxidative stress, left ventricular function, various molecular analyses, as well as pathological and structural myocardial changes. Results: Hexarelin treatment improved contractile function and attenuated myocardial histopathological damages, oxidative stress, fibrosis, as well as apoptosis. All these were accompanied by the upregulation of myocardial eNOS and an increase in serum NO concentration. Conclusion: As evidenced by the obtained results, the anti-cardiac failure capacity of hexarelinin in a rat model is mediated by an increase in serum nitric oxide level and the up-modulation of myocardial eNOS; therefore, they can be considered therapeutic targets against heart failure.