Nitric oxide production during Vibrio cholerae infection

Edward N. Janoff, Hiroshi Hayakawa, David N. Taylor, Claudine E. Fasching, Julie R. Kenner, Edgar Jaimes, Leopoldo Raij

Research output: Contribution to journalArticlepeer-review


Vibrio cholerae induces massive intestinal fluid secretion that continues for the life of the stimulated epithelial cells. Enhanced regional blood flow and peristalsis are required to adapt to this obligatory intestinal secretory challenge. Nitric oxide (NO) is a multifunctional molecule that modulates blood flow and peristalsis and possesses both cytotoxic and antibacterial activity. We demonstrate that, compared with those in asymptomatic control subjects, levels of stable NO metabolites (NO2/-/NO3) are significantly increased in sera from acutely ill Peruvian patients with natural cholera infection as well as from symptomatic volunteers from the United States infected experimentally with V. cholerae. In a rabbit ileal loop model in vivo, cholera toxin (CT) elicited fluid secretion and dose-dependent increases in levels of NO2/NO3/- in the fluid (P < 0.01). In contrast, lipopolysaccharide (LPS) elicited no such effects when applied to the intact mucosa. NO synthase (NOS) catalytic activity also increased in toxin-exposed tissues (P < 0.05), predominantly in epithelial cells. The CT-induced NOS activity was Ca2+ dependent and was not suppressed by dexamethasone. In conclusion, symptomatic V. cholerae infection induces NO production in humans. In the related animal model, CT, but not LPS, stimulated significant production of NO in association with increases in local Ca2+-dependent NOS activity in the tissues.

Original languageEnglish (US)
Pages (from-to)G1160-G1167
JournalAmerican Journal of Physiology - Gastrointestinal and Liver Physiology
Issue number5 36-5
StatePublished - 1997
Externally publishedYes


  • Epithelial cells
  • Innate intestinal immunity
  • Mucosal response to infection

ASJC Scopus subject areas

  • Physiology
  • Hepatology
  • Gastroenterology
  • Physiology (medical)


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