Berberine attenuates angiotensin Ⅳ-induced cardiomyocyte hypertrophy via activation of PPARα/NO signaling pathway

Myocardial hypertrophy is a common pathological process of many cardiovascular diseases and is the structural basis for the occurrence of heart failure. Berberine, one of the main ingredients of Rhizoma coptidis and Cortex Phellodendri , is an isoquinoline alkaloid with multiple pharmacological applications, especially in cardiovascular diseases. The aim of this study was to investigate the role of berberine on cardiomyocyte hypertrophy induced by angiotensin Ⅳ via PPARα/NO signal pathway. The cardiomyocyte hypertrophy induced by angiotensin Ⅳ (1 nmol/L) was characterized by increasing in the cell surface area, protein content, and atrial natriuretic factor mRNA expression level. The results showed that angiotensin IV could not only significantly induce cardiomyocyte hypertrophy, but also decrease the expressions of PPARα at both mRNA and protein levels, which occurred in parallel with an declining in the eNOS mRNA expression and NOS activity, as well as NO concentration. However, these effects were obviously inhibited by berberine (from 10 to 100 µmol/L). Both MK886 (0.3 µmol/L), a selective PPARα antagonist, and N G -nitro- L -arginine-methyl ester (100 µmol/L), a NOS inhibitor, could abolish the effects of berberine. The results suggested that berberine may have important implications in anti- angiotensin Ⅳ-induced cardiomyocyte hypertrophy via PPARα/NO signaling pathway .