title: Alcohol does not modulate the augmented acetylcholine-induced vasodilatory response in hemorrhaged rodents.
abstract: Our previous studies have shown that acute alcohol intoxication (AAI) decreases blood pressure, exacerbates hypotension after hemorrhagic shock, impairs the pressor response to fluid resuscitation, and blunts neuroendocrine activation. We hypothesized that impaired hemodynamic compensation during and after hemorrhagic shock in the acute alcohol-intoxicated host is the result of blunted neuroendocrine activation or, alternatively, of an impaired vascular responsiveness to vasoactive agents. The aim of this study was to examine the effects of AAI, AAI and hemorrhagic shock, and AAI and hemorrhagic shock and resuscitation on reactivity of isolated blood vessel rings to phenylephrine and acetylcholine. Chronically instrumented, conscious male Sprague-Dawley rats (300-350 g) received a primed continuous 15-h intragastric alcohol infusion (2.5 g x kg(-1) + 300 mg x kg(-1) x h(-1)), and time-matched controls received an isocaloric-isovolumic dextrose infusion. At completion of infusions, animals were randomized to sham, 60-min fixed-pressure hemorrhage, or hemorrhagic shock followed by resuscitation with lactated Ringer's solution. At the completion of the experimental protocols, animals were killed, and thoracic aorta and mesenteric artery ring segments (1-2 mm) were prepared and studied in myograph baths. Acute alcohol intoxication did not produce significant alterations in either pressor or dilator responses in aortic or mesenteric rings. These findings suggest that impaired hemodynamic counterregulation during hemorrhagic shock in AAI is not due to decreased vasopressor responsiveness. However, our results suggest a role for accentuated vasodilatory responses that may be central in progression to decompensatory shock.
authors.affiliation: Department of Physiology and Alcohol and Drug Abuse Center of Excellence, LSU Health Sciences Center, New Orleans, Louisiana 70112, USA.
authors.forename: Miguel F
authors.initials: MF
authors.lastname: Molina
authors.forename: Annie
authors.initials: A
authors.lastname: Whitaker
authors.forename: Patricia E
authors.initials: PE
authors.lastname: Molina
authors.forename: Kathleen H
authors.initials: KH
authors.lastname: McDonough
mesh_terms: D000109:Acetylcholine / Q000378:metabolism / Q000494:pharmacology*; D000435:Alcoholic Intoxication / Q000503:physiopathology; D000818:Animals; D001013:Aorta, Thoracic / Q000473:pathology; D002492:Central Nervous System Depressants; D004305:Dose-Response Relationship, Drug; D000431:Ethanol / Q000494:pharmacology; D006470:Hemorrhage / Q000628:therapy*; D008297:Male; D010656:Phenylephrine / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012151:Resuscitation / Q000379:methods; D012769:Shock / Q000188:drug therapy; D014664:Vasodilation / Q000187:drug effects*
chemical_list: D002492:Central Nervous System Depressants; D010656:Phenylephrine; D000431:Ethanol; D000109:Acetylcholine