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Nitric oxide synthesis in patients with infective gastroenteritis
  1. P Fortea,
  2. R S Dykhuizenb,
  3. E Milnec,
  4. A McKenzieb,
  5. C C Smithb,
  6. N Benjamina
  1. aDepartment of Clinical Pharmacology, St Bartholomew’s and the Royal London School of Medicine and Dentistry, London, UK, bInfection Unit, Aberdeen Royal Infirmary, Foresterhill, Aberdeen, UK, cRowett Research Institute, Greenburn Road, Bucksburn, Aberdeen, UK
  1. Dr P Forte, Department of Clinical Pharmacology, St Bartholomew’s and the Royal London School of Medicine and Dentistry, Charterhouse Square, London EC1M 6BQ, UK.

Abstract

BACKGROUND There is evidence that endogenous nitrate synthesis is notably increased in patients with infective gastroenteritis.

AIMS To determine whether this is due to nitric oxide (NO) production via the l-arginine/NO pathway.

METHODS Seven male patients with community acquired bacterial gastroenteritis and 15 healthy male volunteers participated in this study. All patients had stool culture positive infective gastroenteritis. A bolus of 200 mgl-[15N]2-arginine was administered intravenously after an overnight fast. Urine was collected for the next 36 hours. Urinary [15N:14N]nitrate ratio was assessed by dry combustion in an isotope ratio mass spectrometer.

RESULTS Mean 36 hour total urinary nitrate excretion in the gastroenteritis group was 5157 (577) μmol compared with 2594 (234) μmol in the control group (p<0.001). Thirty six hour urinary [15N]nitrate excretion was considerably higher in the gastroenteritis group compared with the control group (13782 (1665) versus 1698 (98) ηmol; p<0.001). These values represent 1.129 (0.139)% and 0.138 (0.007)% of [15N]nitrogen administered (p<0.001), respectively. Corrected 36 hour urinary [15N]nitrate excretion for urinary creatinine was also significantly higher in the patient compared with the control group (1934 (221) versus 303 (35) ηmol/mmol; p<0.001).

CONCLUSION Results show notably enhanced nitrate synthesis due to increased activity of thel-arginine/NO pathway in patients with infective gastroenteritis.

  • endothelium derived relaxing factor
  • l-[15N]2-arginine
  • nitrates
  • infection
  • diarrhoea
  • Abbreviations used in this paper

    LPS
    lipopolysaccharide
    IBD
    inflammatory bowel disease
    NO
    nitric oxide
    NOS
    nitric oxide synthase
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  • Abbreviations used in this paper

    LPS
    lipopolysaccharide
    IBD
    inflammatory bowel disease
    NO
    nitric oxide
    NOS
    nitric oxide synthase
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