Nitric oxide-derived urinary nitrate as a marker of intestinal bacterial translocation in rats.
OBJECTIVE
Bacterial translocation across the gut wall may lead to bacteremia and sepsis. Bacteriological analyses are laborious and time consuming, which precludes a rapid diagnosis of bacterial translocation. Synthesis of nitric oxide by macrophages is a primary response to bacterial infections. Therefore, the aim of this study was to examine whether NO-derived nitrate excretion in urine can be used as a rapid and quantitative marker of intestinal bacterial translocation.


METHODS
The kinetics of urinary nitrate excretion was determined in rats intraperitoneally injected with increasing doses of Salmonella enteritidis lipopolysaccharide. Subsequently, the response to bacterial translocation was studied in rats infected orally with different doses of viable, invasive S. enteritidis.


RESULTS
Increasing the lipopolysaccharide dose from 0.05 to 0.50 mg/kg resulted in a transient, dose-dependent, almost 10-fold increase in urinary nitrate excretion. Administration of the NO synthase inhibitor NG-nitro-L-arginine methyl ester merely inhibited the increase in nitrate excretion after lipopolysaccharide injection. Increasing the infective dose of viable Salmonella resulted in a time- and dose-dependent exponential increase in nitrate output. Translocation was a prerequisite for provoking a nitrate response. Total urinary nitrate excretion after infection and classical infection parameters, such as weight of the mesenteric lymph nodes and population levels of Salmonella in feces, were highly correlated.


CONCLUSIONS
Urinary nitrate excretion is a quantitative, noninvasive biomarker of intestinal bacterial translocation, which can be used to follow the course of a systemic infection.
Department of Nutrition, Netherlands Institute for Dairy Research, Ede.
I M
IM
Oudenhoven
H L
HL
Klaasen
J A
JA
Lapré
A H
AH
Weerkamp
R
R
Van der Meer
D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives / Q000494:pharmacology; D015415:Biomarkers / Q000652:urine; D004305:Dose-Response Relationship, Drug; D005243:Feces / Q000382:microbiology; D007422:Intestines / Q000382:microbiology*; D008070:Lipopolysaccharides / Q000378:metabolism / Q000494:pharmacology; D008198:Lymph Nodes / Q000473:pathology; D008264:Macrophages / Q000378:metabolism; D008297:Male; D019331:NG-Nitroarginine Methyl Ester; D009566:Nitrates / Q000652:urine*; D009569:Nitric Oxide / Q000032:analysis* / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D012481:Salmonella Infections, Animal / Q000175:diagnosis / Q000473:pathology / Q000652:urine; D012477:Salmonella enteritidis / Q000302:isolation & purification* / Q000378:metabolism; D013997:Time Factors
D015415:Biomarkers; D008070:Lipopolysaccharides; D009566:Nitrates; D009569:Nitric Oxide; D001120:Arginine; D019331:NG-Nitroarginine Methyl Ester