Time-dependent aggravation or attenuation of lipopolysaccharide-induced gastric injury by nitric oxide synthase inhibition

James W. Suliburk, Kenneth S. Helmer, Sasha D. Kennison, David W Mercer, Emily K. Robinson

Research output: Contribution to journalArticle

9 Citations (Scopus)

Abstract

Background. This study was conducted to test the hypothesis that nonselective nitric oxide synthase (NOS) inhibitors have different effects on lipopolysaccharide (LPS)-induced gastric injury depending upon whether they are given concurrently with LPS or after LPS at a time point that inducible NOS is up-regulated. Materials and methods. Female Sprague-Dawley rats received intraperitoneal (IP) LPS (20 mg/kg) for 3 h. Western immunoblot was used to determine iNOS, eNOS, and nNOS immunoreactivity after 3 h. In an additional set of experiments, we assessed the time dependent effects of nitric oxide synthase inhibition by giving rats LPS (20 mg/kg, IP) concurrently with Nitro-l-arginine methyl ester (l-NAME; 2-5 mg/kg, SC) or l-NG-(1-iminoethyl) lysine (l-NIL; 10 mg/kg, IP) for 5 h or LPS and delayed administration of l-NAME or l-NIL 3 h following LPS injection in identical doses. For these NOS inhibition experiments microscopic and macroscopic injury was assessed by a blinded observer using previously published scoring systems. Injury studies were conducted by exposing the stomach to 3 ml of 5 mM acidified taurocholate for 5 minutes in an anesthetized prep. Results. A 3-h treatment with LPS (20 mg/kg IP) significantly increased iNOS protein immunoreactivity (Western immunoblot) but not eNOS or nNOS. NG-l-NAME (2-5 mg/kg SC) dose dependently aggravated macroscopic (computerized planimetry) and morphological gastric injury caused by the intraluminal bile irritant 5 mm acidified taurocholate for 10 min when given concurrently with LPS, an effect reversed by l- but not D-arginine (300 mg/kg). In contrast, delayed administration of l-NAME (3 h after LPS) dose dependently attenuated the ability of LPS to exacerbate gastric injury from bile. Both concurrent and delayed administration of the selective iNOS inhibitor, l-NIL (10 mg/kg IP) attenuated the effects of LPS. Conclusions. These data indicate that during endotoxemia, the stomach is rendered more susceptible to damage from luminal irritants such as bile, a frequent occurrence in septic patients with a gastrointestinal ileus. In this setting, iNOS has a pathologic role while the constitutive NOS isoforms play gastroprotective roles.

Original languageEnglish (US)
Pages (from-to)265-271
Number of pages7
JournalJournal of Surgical Research
Volume129
Issue number2
DOIs
StatePublished - Dec 1 2005

Fingerprint

Nitric Oxide Synthase
Lipopolysaccharides
Stomach
Wounds and Injuries
Bile
Taurocholic Acid
Irritants
Western Blotting
Endotoxemia
Ileus
Nitric Oxide Synthase Type II
Lysine
Sprague Dawley Rats
Arginine
Protein Isoforms
Injections

Keywords

  • Gastric injury
  • LPS
  • Nitric oxide synthase
  • Rat
  • Stomach
  • eNOS
  • iNOS
  • nNOS

ASJC Scopus subject areas

  • Surgery
  • Medicine(all)

Cite this

Time-dependent aggravation or attenuation of lipopolysaccharide-induced gastric injury by nitric oxide synthase inhibition. / Suliburk, James W.; Helmer, Kenneth S.; Kennison, Sasha D.; Mercer, David W; Robinson, Emily K.

In: Journal of Surgical Research, Vol. 129, No. 2, 01.12.2005, p. 265-271.

Research output: Contribution to journalArticle

Suliburk, James W. ; Helmer, Kenneth S. ; Kennison, Sasha D. ; Mercer, David W ; Robinson, Emily K. / Time-dependent aggravation or attenuation of lipopolysaccharide-induced gastric injury by nitric oxide synthase inhibition. In: Journal of Surgical Research. 2005 ; Vol. 129, No. 2. pp. 265-271.
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