title: The effect of alpha-adrenergic antagonism upon nitrogen loss during endotoxemia.
abstract: Sixty male Sprague-Dawley rats were randomized to receive parenteral nutrition (PN) only; PN plus continuous infusion of Escherichia coli 026:B6 lipopolysaccharide (PN + LPS) at 6 mg.kg-1.d-1; or PN plus LPS plus a continuous infusion of the alpha-adrenergic antagonist phentolamine (PN + LPS + PHEN) at 5 mg.kg-1.d-1 or 20 mg.kg-1.d-1 for 48 h. All animals received isocaloric, isonitrogenous PN. LPS significantly lowered nitrogen balance (mmol/48 h) from PN control; however, addition of PHEN substantially worsened nitrogen balance compared with LPS (14.2 +/- 3, 2.4 +/- 5.2, -1.6 +/- 4.5, -0.8 +/- 5.4, for the PN, PN + LPS, PN + LPS + PHEN5 and PN + LPS + PHEN20 groups, respectively; P < 0.0001). Urinary 3-methylhistidine/creatinine ratio (3-meH/creat) paralleled the nitrogen balance data (0.30 +/- 0.09, 0.45 +/- 0.12, 0.51 +/- 0.14, 0.60 +/- 0.12, respectively; P < 0.0001). The high-dose PHEN resulted in 82 +/- 9% blockade. To ascertain if any beneficial effect upon body protein loss is achieved during severe stress, 30 rats were given PN + LPS at 12 mg.kg-1.d-1 or PN + LPS12 + PHEN20. These data showed similar changes in nitrogen balance and 3-methylhistidine/creatinine with the use of PHEN during severe endotoxemia. alpha-adrenergic antagonism with PHEN worsens body protein loss as measured by nitrogen balance and 3-methylhistidine/creatinine in PN-fed endotoxemic rats.
authors.affiliation: Department of Clinical Pharmacy, University of Tennessee-Memphis 38163, USA.
authors.forename: R N
authors.initials: RN
authors.lastname: Dickerson
authors.forename: D A
authors.initials: DA
authors.lastname: Kuhl
authors.forename: R O
authors.initials: RO
authors.lastname: Brown
authors.forename: J T
authors.initials: JT
authors.lastname: Methvin
authors.forename: J F
authors.initials: JF
authors.lastname: Mouser
authors.forename: E B
authors.initials: EB
authors.lastname: Hak
authors.forename: L J
authors.initials: LJ
authors.lastname: Hak
mesh_terms: D000317:Adrenergic alpha-Antagonists / Q000008:administration & dosage / Q000494:pharmacology*; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects / Q000502:physiology*; D015331:Cohort Studies; D004305:Dose-Response Relationship, Drug; D019446:Endotoxemia / Q000139:chemically induced / Q000503:physiopathology*; D004926:Escherichia coli; D007262:Infusions, Intravenous; D008070:Lipopolysaccharides / Q000008:administration & dosage; D008297:Male; D008762:Methylhistidines / Q000652:urine; D008934:Mitogens / Q000008:administration & dosage; D009584:Nitrogen / Q000378:metabolism*; D010288:Parenteral Nutrition / Q000379:methods*; D010646:Phentolamine / Q000008:administration & dosage / Q000494:pharmacology*; D010656:Phenylephrine / Q000008:administration & dosage / Q000494:pharmacology; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D000317:Adrenergic alpha-Antagonists; D008070:Lipopolysaccharides; D008762:Methylhistidines; D008934:Mitogens; C036757:lipopolysaccharide B; D010656:Phenylephrine; C028118:3-methylhistidine; D009584:Nitrogen; D010646:Phentolamine