Role and regulation of calcineurin in angiotensin II-stimulated cardiac myocyte hypertrophy of rats

AIM: To study the role and regulation of calcineurin(CaN) in angiotensin II(AngⅡ)-stimulated cardiacmyocyte hypertrophy of rats. METHODS: Using AngⅡ to induce the cultured cardiac myocyte hypertrophy of rats, and investigating the effect of CaN inhibitor on [ 3H]-leucine incorporation of AngⅡ-stimulated cardiomyocytes and the regulation of various factors on CaN activity in cardiomyocytes.RESULTS: AngⅡ can stimulate the CaN activity in cultured neonatal rat cardiomyocytes in a dose- and time-dependent manner. In cardiac myocytes incubated with 10, 100, 1000 nmol·L -1 of AngⅡ for 12h, the CaN activities increased respectively by 13%,57%( P0.05 ) and 228%( P 0.01) compared with that in non-stimulated cardiomyocytes. The CaN activities in AngⅡ-stimulated cardiomyocytes were significantly inhibited by losartan(50 μmol·L -1 ), H 7(50 μmol·L -1 )and Fura-2/AM(4 μmol·L -1 ),while no effect was observed with PD98059(50 μmol·L -1 ). The [ 3H]-leucine incorporation in AngⅡ-stimulated cardiomyocytes increased by 46%( P 0.01) compared with that in control group, which was dramatically inhibited by cyclosporin A(0.5～5 μg/mL). CONCLUSIONS: Calcineurin, a Ca 2+ /calmodulin-dependent protein phosphatase, may play an important role in AngⅡ-induced cardiac myocyte hypertrophy. The activation of CaN may dependent on the sustained increases of [Ca 2+ ]i and be regulated by some protein kinases (such as PKC,etc.).