Abstract
Background: Apelin (AP) is the endogenous vasoactive ligand of APJ receptor. It is widely expressed in the heart and lungs and has important cardiovascular functions such as endothelium-dependent vasodilatation and positive inotropic effect. However, the role of apelin-APJ system in pulmonary hypertension (PH) remains to be clarified. Objective: To evaluate the chronic effects of apelin in: right ventricular (RV) myocardial function; cardiac expression of apelin and APJ in healthy and MCT-PH rats Methods: Male Wistar rats were randomly injected with MCT (60mg/Kg, sc) or vehicle (CTR, day 0). One week later, half of these animals were randomly treated with Pyr-apelin-13 (200μg/Kg/day, ip) or a similar volume of vehicle. The study resulted in 4 groups: CTR; AP; MCT and MCT+ AP. At day 24, animals were instrumented to record RV peak systolic (Pmax) pressures, dP/dtmax, dP/dtmin and time constant Tau. Also, heart and lungs were weighted and transmural RV samples were collected for relative quantification of mRNA by real-time RT-PCR. Results are on table . Conclusions: In healthy rats, exogenous apelin potentiates its endogenous production with no significant changes in APJ. MCT-induced PH resulted in a significant down-regulation of apelin-APJ system, which might play a role in the systolic and diastolic dysfunction observed in this model. This down-regulation was completely reverted by chronic administration of exogenous apelin. Therefore, apelin upregulates the cardiac apelin-APJ system exerting beneficial effects on cardiac remodeling and function, namely, by decreasing PH, RV diastolic function and hypertrophy. These results reveal the importance of apelin-APJ system in the pathophysiology of PH, suggesting that apelin is a potential therapeutic target in this disease. Results table
Published Version
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