The Protective Effects of Metoprolol Against Arginine Vasopressin (AVP)-Induced Cellular Senescence in Cardiomyocytes

Cellular senescence of cardiomyocytes is reported to be involved in the pathological mechanism of cardiac diseases. Metoprolol is a blocker of β1 receptor used for the treatment of hypertension, which is recently reported to protect cardiomyocytes from injury. The present study aims to investigate the protective effects of Metoprolol against Arginine vasopressin (AVP)-induced cellular senescence in cardiomyocytes. CCK-8 and LDH release assays were used to evaluate cytotoxicity. ELISA was used to detect the release of 8OHdG. SA-β-gal activity and telomerase activity were measured to index cell senescence. The iNampt activity, NAD+/NADPH ratio, and Sirt1 activity were detected by commercial kits. Levels of acetylated p53 were measured by immunoprecipitation and the expression of p21 was determined by RT-PCR and western blot analysis. We found that the elevated level of 8OHdG, percentage of SA-β-gal positive cells, and decreased telomerase activity induced by AVP were significantly reversed by the treatment of Metoprolol. Metoprolol elevated the suppressed iNampt activity, NAD+/NADPH ratio, and Sirt1 activity in cardiomyocytes challenged with AVP. The upregulated expression of acetylated p53 and p21 induced by AVP were dramatically downregulated by the presence of Metoprolol. Taken together, our data revealed that Metoprolol protected the cell senescence in cardiomyocytes induced by AVP.