Attenuating effects of dihydromyricetin on angiotensin II-induced rat cardiomyocyte hypertrophy related to antioxidative activity in a NO-dependent manner

Abstract

Context: Dihydromyricetin (DMY) displays a range of biological properties However, whether DMY attenuates cardiomyocyte hypertrophy is unknown. Objective: To investigate whether DMY had potential therapeutic value to protect against angiotensin II (Ang II)-induced cardiomyocyte hypertrophy. Materials and methods: Neonatal rat cardiomyocytes were pretreated with DMY (0-320M) followed with Ang II (100nM) stimulation for 24h, and then degree of hypertrophy was evaluated by cell surface analysis. Levels of reactive oxygen species (ROS) were measured with 2′,7′-dichlorfluorescein-diacetate (DCFH-DA) fluorescent staining. Antioxidative activity was evaluated by malondialdehyde (MDA) level, superoxide dismutase (SOD) activity, and total antioxidant capacity (T-AOC). Cyclic guanosine monophosphate (cGMP) was determined with a radioimmunoassay. Results: Pre-incubation with DMY (20, 40, 80, and 160M) for 8h, 12h, 24h, or 48h decreased cell surface areas. It down-regulated mRNA expression of atrial natriuretic factor (1.95- to 1.24-fold) and -myosin heavy chains (3.51- to 2.32-fold), reduced levels of MDA as well as increased SOD activity and T-AOC. Expression of SOD and thioredoxin were enhanced by DMY, whereas p22phox and phosphorylation of mitogen-activated protein kinases were inhibited. Content of cGMP (0.54- to 0.80-fold) and phosphorylation of endothelial nitric oxide synthase at serine 1177 (0.70- to 1.05-fold) were augmented by DMY. Moreover, attenuating effect of DMY on hypertrophy was abolished when NO production was inhibited by l-NAME. Conclusion: Attenuating effects of DMY on Ang II-induced cardiomyocyte hypertrophy related to antioxidative activity in a NO-dependent manner.