CYCLIC-AMP AUGMENTS CYTOKINE-STIMULATED NITRIC-OXIDE SYNTHESIS IN RATCARDIAC MYOCYTES

We investigated the effect of adenosine 3',5'-cyclic monophosphate (cA MP) on inducible nitric oxide synthase (iNOS) expression in cultured n eonatal rat cardiac myocytes. Incubation of cardiac myocytes for 24 h with interleukin-1 beta (IL-1 beta) caused a significant increase in t he production of nitrite, a stable metabolite of nitric oxide. Dibutyl cAMP (db-cAMP) significantly augmented nitrite production by IL-1 bet a-stimulated, but not by unstimulated cells, in a dose-dependent manne r. db-cAMP also dose dependently increased nitrite production by tumor necrosis factor-alpha(TNF-alpha)-stimulated cells. Simultaneous incub ation with N-G-monomethyl-L-arginine completely inhibited the effect o f db-cAMP on nitrite production. cAMP-induced nitrite production by cy tokine-stimulated cells was accompanied by increased iNOS mRNA accumul ation. The synergistic effect of cAMP on IL-1 beta-induced nitrite acc umulation was mimicked by cAMP-generating agonists forskolin and isopr oterenol. These results indicate that cAMP upregulates cytokine-induce d iNOS expression in cardiac myocytes. (C) 1996 Academic Press Limited