title: Opiate modulation of hemodynamic, hormonal, and cytokine responses to hemorrhage.
abstract: The aim of the present study was to examine the role of opiate receptor activation in modulating the hemodynamic, neuroendocrine, and tissue (lung and spleen) cytokine responses to fixed pressure (40 mm Hg) hemorrhage. Chronically catheterized, conscious unrestrained non-heparinized male Sprague-Dawley rats were pretreated with either naltrexone (15 mg/kg intraperitoneally in 0.5 mL of saline) or saline (0.5 mL) 15 min prior to hemorrhage followed by fluid resuscitation with Ringer's lactate. Animals were sacrificed at completion of the 60-min resuscitation period. Blood loss required to achieve mean arterial blood pressure (MABP) of 40 mm Hg was higher in naltrexone-treated animals than in time-matched saline controls (4.4+/-0.2 versus 3.7+/-0.2 mL/100 g BW, P< 0.05). Hemorrhage increased plasma levels of corticosterone (30%) and ACTH (3-fold) within 15 min. Naltrexone prevented the hemorrhage-induced rise in corticosterone without affecting the rise in ACTH. Hemorrhage increased beta-endorphin levels (4-fold) and produced an immediate (5 min) and progressive increase in circulating epinephrine and norepinephrine levels reaching values that were 50- and 20-fold, respectively, higher than basal. Pre-treatment with naltrexone did not alter the time course or magnitude of the hemorrhage-induced increases in plasma beta-endorphin or catecholamines. Hemorrhage increased lung and spleen content of TNF (60%), IL-1alpha (300%), IL-6 (40%-60%), and IL-10 (80%) above values of time-matched sham control animals. Pre-treatment with naltrexone blunted the magnitude of the increases in tissue cytokine content in response to a given blood loss. These results indicate that endogenous opiates modulate the hemodynamic instability, neuroendocrine, and cytokine responses to hemorrhagic shock.
authors.affiliation: Department of Physiology Louisiana State University Health Sciences Center, New Orleans 70112, USA.
authors.forename: P E
authors.initials: PE
authors.lastname: Molina
mesh_terms: D000324:Adrenocorticotropic Hormone / Q000097:blood; D000818:Animals; D017209:Apoptosis; D001794:Blood Pressure / Q000187:drug effects; D003345:Corticosterone / Q000097:blood; D016207:Cytokines / Q000378:metabolism*; D004195:Disease Models, Animal; D006439:Hemodynamics / Q000187:drug effects / Q000502:physiology*; D007375:Interleukin-1 / Q000378:metabolism; D016753:Interleukin-10 / Q000378:metabolism; D015850:Interleukin-6 / Q000378:metabolism; D008168:Lung / Q000187:drug effects / Q000276:immunology*; D008297:Male; D009271:Naltrexone / Q000494:pharmacology*; D009292:Narcotic Antagonists / Q000494:pharmacology; D009504:Neutrophils / Q000502:physiology; D009195:Peroxidase / Q000032:analysis; D051381:Rats; D017207:Rats, Sprague-Dawley; D012151:Resuscitation; D012771:Shock, Hemorrhagic / Q000097:blood / Q000276:immunology / Q000503:physiopathology*; D013154:Spleen / Q000187:drug effects / Q000276:immunology*; D013997:Time Factors; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D001615:beta-Endorphin / Q000097:blood*
chemical_list: D016207:Cytokines; D007375:Interleukin-1; D015850:Interleukin-6; D009292:Narcotic Antagonists; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10; D009271:Naltrexone; D001615:beta-Endorphin; D000324:Adrenocorticotropic Hormone; D009195:Peroxidase; D003345:Corticosterone