Norepinephrine-stimulated MAP kinase activity enhances cytokine-induced NO production by rat cardiac myocytes.
The effect of norepinephrine (NE) on cytokine-stimulated nitric oxide (NO) production by cardiac myocytes has not been previously reported. NE alone caused no significant increase in NO-2 levels over vehicle. Addition of NE to interleukin-1beta (IL-1beta) significantly increased inducible NO synthase (iNOS) mRNA expression, iNOS protein, and NO-2 production vs. IL-1beta alone. Addition of the alpha-adrenergic blocker prazosin or the beta-adrenergic blocker propranolol partially reduced the NE-mediated increase in iNOS mRNA expression and NO-2 production. Addition of prazosin and propranolol together completely abolished the NE-induced increase in iNOS mRNA expression and NO-2 production. NE significantly enhanced mitogen-activated protein (MAP) kinase activity that was reduced by prazosin, propranolol, and PD-98059, a selective MAP kinase kinase inhibitor. Addition of PD-98059 reduced the NE-mediated increase in iNOS mRNA expression and NO-2 production. We report for the first time that NE enhances IL-1beta-stimulated NO production by activation of alpha- and beta-adrenergic receptors through a novel MAP kinase mechanism.
Kan
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Department of Medicine, Morgantown, West Virginia 26506-9157, USA.
Xie
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Finkel
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MS
D000316:Adrenergic alpha-Agonists / Q000494:pharmacology*; D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology; D000318:Adrenergic beta-Agonists / Q000494:pharmacology*; D000319:Adrenergic beta-Antagonists / Q000494:pharmacology; D000818:Animals; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005419:Flavonoids / Q000494:pharmacology; D007375:Interleukin-1 / Q000494:pharmacology*; D009206:Myocardium / Q000166:cytology / Q000378:metabolism*; D009569:Nitric Oxide / Q000037:antagonists & inhibitors / Q000096:biosynthesis*; D019001:Nitric Oxide Synthase / Q000235:genetics / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II; D009638:Norepinephrine / Q000494:pharmacology*; D011224:Prazosin / Q000494:pharmacology; D011433:Propranolol / Q000494:pharmacology; D012333:RNA, Messenger / Q000037:antagonists & inhibitors / Q000378:metabolism; D051381:Rats
D000316:Adrenergic alpha-Agonists; D000317:Adrenergic alpha-Antagonists; D000318:Adrenergic beta-Agonists; D000319:Adrenergic beta-Antagonists; D004791:Enzyme Inhibitors; D005419:Flavonoids; D007375:Interleukin-1; D012333:RNA, Messenger; D009569:Nitric Oxide; D011433:Propranolol; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; C496318:Nos2 protein, rat; D017871:Calcium-Calmodulin-Dependent Protein Kinases; C093973:2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one; D009638:Norepinephrine; D011224:Prazosin