Protective roles of nitric oxide and testosterone in endotoxemia: Evidence from NOS-2-deficient mice

Victor E. Laubach, Patricia L. Foley, Kim S. Shockey, Curtis G. Tribble, Irving L. Kron

Research output: Contribution to journalArticle

49 Scopus citations

Abstract

Lipopolysaccharide (LPS)-induced septic shock, which triggers nitric oxide (NO) overproduction, multiple organ dysfunction, and death, can be affected by gender and sex hormones. We hypothesized that NO is beneficial during endotoxemia and that this beneficial effect is influenced by sex hormones. C57BL/6 wild-type (WT) mice and congenic inducible NO synthase knockout (KO) mice were injected with LPS, and mortality was recorded for 4 days. After 5 mg/kg LPS, female KO mice had significantly higher mortality than WT. After 12.5 mg/kg LPS, both male and female KO mice had significantly higher mortality than WT. Ovariectomy did not alter mortality, but orchiectomy dramatically increased mortality in KO mice. After 5 mg/kg LPS, exogenous testosterone completely prevented the increased mortality in KO female and orchiectomized KO male mice. WT survival was not affected by exogenous testosterone. After 12.5 mg/kg LPS, exogenous testosterone significantly improved survival of female KO mice. Serum enzymes and organ edema, which may not correlate with mortality, were significantly and similarly increased in both WT and KO endotoxemic mice; however, edema was not observed in KO hearts. Thus, NO plays a protective role in endotoxemia while having differential effects on different organs. Importantly, testosterone is beneficial in endotoxemia when NO production is deficient, and may be therapeutic in certain septic patients.

Original languageEnglish (US)
Pages (from-to)H2211-H2218
JournalAmerican Journal of Physiology - Heart and Circulatory Physiology
Volume275
Issue number6 44-6
Publication statusPublished - Dec 1 1998
Externally publishedYes

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Keywords

  • Endotoxin
  • Inducible nitric oxide synthase
  • Knockout mouse
  • Lipopolysaccharide
  • Sepsis
  • Septic shock

ASJC Scopus subject areas

  • Physiology
  • Cardiology and Cardiovascular Medicine
  • Physiology (medical)

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