Cyclic AMP augments cytokine-stimulated nitric oxide synthesis in rat cardiac myocytes.
We investigated the effect of adenosine 3', 5'-cyclic monophosphate (cAMP) on inducible nitric oxide synthase (iNOS) expression in cultured neonatal rat cardiac myocytes. Incubation of cardiac myocytes for 24 h with interleukin-1 beta (IL-1 beta) caused a significant increase in the production of nitrite, a stable metabolite of nitric oxide. Dibutyl cAMP (db-cAMP) significantly augmented nitrite production by IL-1 beta-stimulated, but not by unstimulated cells, in a dose-dependent manner. db-cAMP also dose dependently increased nitrite production by tumor necrosis factor-alpha(TNF-alpha)-stimulated cells. Simultaneous incubation with NG-monomethyl-L-arginine completely inhibited the effect of db-cAMP on nitrite production. cAMP-induced nitrite production by cytokine-stimulated cells was accompanied by increased iNOS mRNA accumulation. The synergistic effect of cAMP on IL-1 beta-induced nitrite accumulation was mimicked by cAMP-generating agonists forskolin and isoproterenol. These results indicate that cAMP upregulates cytokine-induced iNOS expression in cardiac myocytes.
Ikeda
U
U
Department of Cardiology, Jichi Medical School, Tochigi, Japan.
Yamamoto
K
K
Ichida
M
M
Ohkawa
F
F
Murata
M
M
Iimura
O
O
Kusano
E
E
Asano
Y
Y
Shimada
K
K
D000818:Animals; D002478:Cells, Cultured; D000242:Cyclic AMP / Q000378:metabolism / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D007375:Interleukin-1 / Q000378:metabolism*; D009206:Myocardium / Q000166:cytology / Q000378:metabolism*; D009569:Nitric Oxide / Q000096:biosynthesis* / Q000378:metabolism; D019001:Nitric Oxide Synthase / Q000378:metabolism; D051381:Rats; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism*; D019323:omega-N-Methylarginine / Q000037:antagonists & inhibitors
D007375:Interleukin-1; D014409:Tumor Necrosis Factor-alpha; D019323:omega-N-Methylarginine; D009569:Nitric Oxide; D000242:Cyclic AMP; D019001:Nitric Oxide Synthase