LAUSR

ABSTRACT Sodium ferulate (SF) is the sodium salt of ferulic acid, which is one of the effective components of Angelica sinensis and Lignsticum chuanxiong, and plays an important role in protecting the cardiovascular system. In this study, myocardial hypertrophy was induced by angiotensin II (Ang II) 0.1 μmol/L in neonatal Sprague-Dawley rat ventricular myocytes. Nine groups were designed, that is, normal, normal administration, model, L-arginine (L-arg 1000 μmol/L), SF (50, 100, 200 μmol/L) group, and NG-nitro-L-arginine-methyl ester (L-NAME) 1500 μmol/L combined with SF 200 μmol/L or L-arg 1000 μmol/L group, respectively. Cardiomyocyte hypertrophy was confirmed by observing histological changes and measurements of cell diameter, protein content and atrial natriuretic factor and β-myosin heavy chain levels of the cells. Notably, SF could inhibit significantly myocardial hypertrophy of neonatal rat cardiomyocytes in a concentration-dependent manner without producing cytotoxicity, and the levels of nitric oxide (NO), nitric oxide synthase (NOS), endothelial nitric oxide synthase (eNOS) and cyclic guanosine monophosphate (cGMP) were increased, but the level of cyclic adenosine monophosphate(cAMP) was decreased in cardiomyocytes. Simultaneously, levels of protein kinase C beta (PKC-β), Raf-1, extracellular regulated protein kinase 1/2 (ERK1/2) were downregulated, while levels of mitogen-activated protein kinase phosphatase-1 were significantly upregulated. All the beneficial effects of SF were blunted by L-NAME. Overall, these findings reveal that SF can inhibit Ang II-induced myocardial hypertrophy of neonatal rat cardiomyocytes, which is closely related to activation of eNOS/NO/cGMP, and inhibition of PKC and mitogen activated protein kinase signaling pathways.