Alpha-2 adrenoceptor blockade protects rats against lipopolysaccharide. Academic Article uri icon

Overview

MeSH

  • Adrenergic alpha-Agonists
  • Animals
  • Creatinine
  • Escherichia coli
  • Hemodynamics
  • Lung
  • Male
  • Peroxidase
  • Quinoxalines
  • Rats
  • Rats, Sprague-Dawley
  • Survival Rate
  • Tumor Necrosis Factor-alpha
  • Xylazine

MeSH Major

  • Adrenergic alpha-Antagonists
  • Lipopolysaccharides
  • Yohimbine

abstract

  • Alpha-2 adrenoceptors are widely distributed in vascular and nonvascular tissue where they mediate diverse physiologic effects. We noted the laboratory anesthetic urethane, which possesses alpha-2 adrenergic blocking activity, protected rats against lethal endotoxemia (1). Therefore, we undertook the present study to examine whether specific alpha-2 adrenoceptor antagonism would protect against lethality and organ injury induced by lipopolysaccharide (LPS). Sprague-Dawley rats were pretreated with doses of the alpha-2 antagonist rauwolscine up to 1 mg/kg, followed by 20 mg/kg LPS. The highest rauwolscine dose decreased mortality from 100% to zero. In contrast, the alpha-2 agonists xylazine or UK 14,304 increased the lethality of a lower, 10-mg/kg dose of LPS from 20% to 80 to 100%. Rauwolscine administered after LPS had no protective effect against mortality. Rauwolscine pretreatment significantly reduced bowel hemorrhage and liver dysfunction induced by 20 mg/kg LPS, but it had no effect on hematologic changes, the rise in plasma creatinine, or lung myeloperoxidase content. Peak tumor necrosis factor-alpha levels were decreased from 1,305 +/- 333 to 493 +/- 155 pg/ml (p < 0.05) in animals pretreated with rauwolscine. Arterial pressure and heart rate was higher after LPS in animals pretreated with rauwolscine. We conclude that alpha-2 adrenergic blockade protects against LPS, either by decreasing tumor necrosis factor-alpha production or through direct effects on the target tissues of endotoxemia.

publication date

  • December 1996

has subject area

  • Adrenergic alpha-Agonists
  • Adrenergic alpha-Antagonists
  • Animals
  • Creatinine
  • Escherichia coli
  • Hemodynamics
  • Lipopolysaccharides
  • Lung
  • Male
  • Peroxidase
  • Quinoxalines
  • Rats
  • Rats, Sprague-Dawley
  • Survival Rate
  • Tumor Necrosis Factor-alpha
  • Xylazine
  • Yohimbine

Research

keywords

  • Journal Article

Identity

Language

  • eng

Digital Object Identifier (DOI)

  • 10.1164/ajrccm.154.6.8970356

PubMed ID

  • 8970356

Additional Document Info

start page

  • 1689

end page

  • 1693

volume

  • 154

number

  • 6 Pt 1