Alpha-adrenergic stimulation enhances inducible nitric oxide synthase expression in rat cardiac myocytes.
We investigated the effects of alpha 1-adrenergic stimulation on nitric oxide (NO) production by cardiac myocytes. Incubation of cultured neonatal rat cardiac myocytes with interleukin-1 beta (IL-1 beta) caused a significant increase in the production of nitrite, a stable metabolite of NO. Addition of phenylephrine significantly augmented nitrite production by IL-1 beta-stimulated but not by unstimulated myocytes in a dose-dependent manner. The effect of phenylephrine was completely abolished in the presence of NG-monomethyl-L-arginine (L-NMMA) or actinomycin D. Northern blotting revealed increased inducible NO synthase mRNA accumulation in cardiac myocytes treated with IL-1 beta and phenylephrine compared with those treated with IL-1 beta alone. After protein kinase C activity was functionally depleted by treating cells with phorbol 12-myristate 13-acetate for 24 h, phenylephrine did not augment IL-1 beta-induced NO production. The effect of phenylephrine was also abolished in the presence of protein kinase C inhibitor calphostin C. These observations suggest that alpha 1-adrenergic stimulation causes an upregulation of cytokine-induced NO production by cardiac myocytes, which is mediated at least partially via activation of protein kinase C.
Ikeda
U
U
Department of Cardiology, Jichi Medical School, Tochigi, Japan.
Murakami
Y
Y
Kanbe
T
T
Shimada
K
K
D000316:Adrenergic alpha-Agonists / Q000494:pharmacology*; D000818:Animals; D002478:Cells, Cultured; D003609:Dactinomycin / Q000494:pharmacology; D015870:Gene Expression; D006352:Heart Ventricles / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D009566:Nitrates / Q000378:metabolism; D019001:Nitric Oxide Synthase / Q000235:genetics / Q000378:metabolism*; D010656:Phenylephrine / Q000494:pharmacology*; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000378:metabolism*; D012333:RNA, Messenger; D051381:Rats; D017207:Rats, Sprague-Dawley; D019323:omega-N-Methylarginine / Q000494:pharmacology
D000316:Adrenergic alpha-Agonists; D009566:Nitrates; D012333:RNA, Messenger; D003609:Dactinomycin; D010656:Phenylephrine; D019323:omega-N-Methylarginine; D019001:Nitric Oxide Synthase; D011493:Protein Kinase C