Carvedilol stimulates nitric oxide synthesis in rat cardiac myocytes

The purpose of this study was to investigate the effects of the beta-adrene rgic blocker carvedilol on nitric oxide (NO) synthesis in cardiac myocytes. We measured the accumulation of nitrite, a stable oxidation product of NO, and the expression of inducible NO synthase (INOS) protein in cultured neo natal rat cardiac myocytes. Incubation of the cultures with interleukin 1 b eta (IL-1 beta: 10 ng/ml) caused a marked increase in nitrite production. A lthough carvedilol alone showed no effect on nitrite accumulation, it signi ficantly enhanced IL-1 beta-induced nitrite production by cardiac myocytes. The effect of carvedilol was completely abolished in the presence of amino guanidine or actinomycin D. The nitrite production enhanced by carvedilol w as accompanied by increased iNOS protein expression. Unlike carvedilol, oth er beta-blockers, namely propranolol, atenolol and arotinolol, did not enha nce IL-1 beta-induced nitrite production. Addition of isoproterenol signifi cantly increased nitrite production by IL-1 beta-stimulated cardiac myocyte s. Atenolol suppressed this isoproterenol-induced nitrite accumulation, whi le carvedilol further increased the nitrite accumulation. These findings in dicate that carvedilol increases NO synthesis in IL-l beta-stimulated rat c ardiac myocytes by a beta-adrenoceptor-independent mechanism. (C) 2000 Acad emic Press.