title: Sympathoadrenal modulation of stress-activated signaling in burn trauma.
abstract: Burn injury stimulates stress-responsive components, p38 mitogen-activated protein kinase (MAPK)/c-Jun N-terminal kinases (JNK)/nuclear factor (NF)-kappaB. p38 MAPK plays a role in postburn cardiomyocyte tumor necrosis factor-alpha secretion and cardiac dysfunction. Since burn trauma increases circulating catecholamine levels, which in turn modulate inflammatory cytokine production, we hypothesized that increased sympathetic activity after major burn trauma may trigger postburn cardiac p38 MAPK activation via an adrenergic receptor-mediated phenomenon. We examined adrenergic receptor populations involved in burn-activated cardiac stress signaling. Sprague Dawley rats were divided into six groups: 1) control, 2) control plus alpha1-adrenergic agonist phenylephrine (2 microg/kg, intravenous), 3) control plus beta-adrenergic agonist isoproterenol (1 microg/kg, intravenous), 4) burn (fluid resuscitation with lactated Ringer's 4 ml/kg/% burn), 5) burn plus alpha1-adrenergic antagonist prazosin (1 mg/kg, by mouth), and 6) burn plus beta-adrenergic antagonist propranolol (3.3 mg/kg, by mouth). Phenylephrine, but not isoproterenol, increased cardiac p38 MAPK/JNK/NF-kappaB activation. Burn trauma activated p38 MAPK, JNK, and NF-kappaB, and this stress response was blocked by either prazosin or propranolol. Thus, stimulation of the adrenergic pathway may constitute one upstream activator of stress response in burn.
authors.affiliation: Department of Surgery, University of Texas Southwestern Medical Center, 5323 Harry Hines Boulevard, Dallas, TX 75390-9160, USA.
authors.forename: Cherry
authors.initials: C
authors.lastname: Ballard-Croft
authors.forename: Jureta W
authors.initials: JW
authors.lastname: Horton
mesh_terms: D000316:Adrenergic alpha-Agonists / Q000494:pharmacology; D000318:Adrenergic beta-Agonists / Q000494:pharmacology; D000818:Animals; D015153:Blotting, Western; D002056:Burns / Q000378:metabolism* / Q000503:physiopathology; D004195:Disease Models, Animal; D004791:Enzyme Inhibitors / Q000494:pharmacology; D007093:Imidazoles / Q000494:pharmacology; D066298:In Vitro Techniques; D007545:Isoproterenol / Q000494:pharmacology; D048031:JNK Mitogen-Activated Protein Kinases; D048670:MAP Kinase Kinase 4; D020929:Mitogen-Activated Protein Kinase Kinases / Q000378:metabolism; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D009200:Myocardial Contraction / Q000187:drug effects*; D009206:Myocardium / Q000378:metabolism*; D016328:NF-kappa B / Q000378:metabolism; D010656:Phenylephrine / Q000494:pharmacology; D011433:Propranolol / Q000494:pharmacology; D011725:Pyridines / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D048051:p38 Mitogen-Activated Protein Kinases
chemical_list: D000316:Adrenergic alpha-Agonists; D000318:Adrenergic beta-Agonists; D004791:Enzyme Inhibitors; D007093:Imidazoles; D016328:NF-kappa B; D011725:Pyridines; D014409:Tumor Necrosis Factor-alpha; D010656:Phenylephrine; D011433:Propranolol; D048031:JNK Mitogen-Activated Protein Kinases; D020928:Mitogen-Activated Protein Kinases; D048051:p38 Mitogen-Activated Protein Kinases; D048670:MAP Kinase Kinase 4; D020929:Mitogen-Activated Protein Kinase Kinases; D007545:Isoproterenol; C093642:SB 203580