title: Cardiovascular Responsiveness to Vasopressin and α1-Adrenergic Receptor Agonists After Burn Injury.
abstract: The effects of burn injury on cardiovascular responsiveness to vasoactive agents are not well understood. The aims of this study were to determine whether burn injury alters cardiovascular reactivity to vasoactive drugs in vivo and intrinsic function of isolated mesenteric resistance arteries. Anesthetized Sprague-Dawley rats were subjected to sham procedure or 30% TBSA dorsal scald burn, followed by crystalloid resuscitation (Parkland Formula). At 24, 72, 96, and 168 hours post burn, rats were reanesthetized, and the mean arterial blood pressure (MAP) responses to various doses of the α1-adrenergic receptor agonist phenylephrine and arginine vasopressin were tested. Mesenteric arteries were harvested from uninjured animals and at 24 and 168 hours post burn. The responsiveness of arteries to phenylephrine and arginine vasopressin was tested by pressure myography. Dose response curves were generated and EC50 concentrations, Hill slopes, and maximal effects were compared. The potency of phenylephrine to increase MAP was reduced 2-fold 24 hours post burn (P < .05 vs sham) and gradually normalized at later time points. The reactivity of isolated arteries to phenylephrine was not significantly altered after burns. The potency of arginine vasopressin to increase MAP and to constrict isolated arteries was increased 2- to 3-fold at 24 hours post burn (P < .05) and normalized at later time points. Our findings suggest that burn injury differentially regulates vasopressor and blood pressure effects of α-adrenergic and vasopressin receptor agonists. Intrinsic vasopressin receptor reactivity of resistance arteries is sensitized early after burns. These findings will help to optimize resuscitation strategies and vasopressor use in difficult to resuscitate burn patients.
authors.affiliation: From the *Department of Surgery, Burn and Shock Trauma Research Institute, and †Department of Molecular Pharmacology and Therapeutics, Loyola University Chicago, Stritch School of Medicine, Maywood, Illinois.
authors.forename: Ann E
authors.initials: AE
authors.lastname: Evans
authors.forename: P Geoff
authors.initials: PG
authors.lastname: Vana
authors.forename: Heather M
authors.initials: HM
authors.lastname: LaPorte
authors.forename: Richard H
authors.initials: RH
authors.lastname: Kennedy
authors.forename: Richard L
authors.initials: RL
authors.lastname: Gamelli
authors.forename: Matthias
authors.initials: M
authors.lastname: Majetschak
mesh_terms: D058668:Adrenergic alpha-1 Receptor Antagonists / Q000008:administration & dosage*; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects*; D002056:Burns / Q000150:complications* / Q000628:therapy; D002319:Cardiovascular System / Q000187:drug effects*; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D007275:Injections, Intravenous; D008297:Male; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D012151:Resuscitation / Q000379:methods*; D016896:Treatment Outcome; D014655:Vascular Resistance / Q000187:drug effects; D014667:Vasopressins / Q000008:administration & dosage*
chemical_list: D058668:Adrenergic alpha-1 Receptor Antagonists; D014667:Vasopressins