Alpha-2 adrenoceptor blockade protects rats against lipopolysaccharide

H. E. Fessler, L. Otterbein, Soon Chung Hee Soon Chung, A. M.K. Choi

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish (US)
Pages (from-to)1689-1693
Number of pages5
JournalAmerican journal of respiratory and critical care medicine
Volume154
Issue number6
DOIs
StatePublished - Jan 1 1996

ASJC Scopus subject areas

  • Pulmonary and Respiratory Medicine
  • Critical Care and Intensive Care Medicine

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