Abstract: 【Objective】 To investigate whether or not SIRT6 prevents phenylephrine -induced cardiomyocyte hypertrophy via eNOS.【Methods】 SIRT6 was overexpressed by adenovirus infection

or was knocked down by RNA interference in primary culture of neonatal rat cardiomyocytes. The mRNA expressions of hypertrophic markers ANF and BNP

the cell surface area

the protein expression of eNOS and production of NO were investigated. 【Results】 SIRT6 overexpression inhibited the increase of ANF and BNP mRNA expressions

and the increase of cell surface area induced by PE (P < 0.05); SIRT6 silencing triggered the expressions of ANF and BNP as compared to the control (P < 0.05)

indicating that SIRT6 prevented PE -induced cardiomyocyte hypertrophy. In addition

SIRT6 overexpression reversed PE -induced down -regulation of NO production and partially inhibited the decrease of eNOS (P < 0.05)

while SIRT6 siRNA suppressed the expression of eNOS and NO production (P < 0.05)

suggesting that SIRT6 regulated the expression and activity of eNOS. Furthermore

the eNOS inhibitor L -NAME blocked the protective effects of SIRT6 on cardiomyocytes hypertrophy (P < 0.05). 【Conclusions】 SIRT6 prevents cardiomyocyte hypertrophy through regulating eNOS.