Roles of nitric oxide synthases in platelet-activating factor-induced intestinal necrosis in rats

Xiao Wu Qu*, Ranna A. Rozenfeld, Wei Huang, Xiaoming Sun, Xiao Di Tan, Wei Hsueh

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

26 Scopus citations

Abstract

Objective: To examine the role of constitutive and inducible nitric oxide synthases (cNOS and iNOS) in platelet-activating factor (PAF)-induced shock and intestinal injury. Design: Prospective, randomized, controlled experimental study. Setting: Hospital research laboratory. Subjects: Young adult male Sprague-Dawley rats were anesthetized and studied. Interventions: Rats were injected with PAF, either alone or after the following pretreatments: a) selective iNOS inhibitors aminoguanidine or S- methylisothiourea; b) 3-morpholinosydnonimine, a NO donor; c) S- methylisothiourea + 3-morpholinosydnonimine; and d) antineutrophil antibody (to deplete neutrophils). Measurements and Main Results: Blood pressure, hematocrit, white blood cell counts, intestinal injury, and intestinal cNOS and iNOS activities were assessed. We found that: a) cNOS is the predominant NOS in the intestine and its activity is inversely correlated to the level of tissue injury; b) there is a time-dependent increase in cNOS activity in sham-operated animals, which was abolished by PAF; c) Western blotting and immunohistochemistry showed iNOS present in the normal intestine, localizing mainly in crypt cells; d) iNOS inhibitors attenuated PAF-induced injury in animals with high cNOS activity, but had no protective effect in animals with low cNOS activity; e) 3-morpholinosydnonimine, alone or together with S- methylisothiourea, alleviated PAF-induced injury; and f) neutrophil depletion blocked the suppressive effect of PAF on cNOS and prevented injury. Conclusions: We conclude that cNOS and iNOS play different roles in PAF- induced intestinal injury. Caution should be exerted concerning potential therapeutic uses of iNOS inhibitors.

Original languageEnglish (US)
Pages (from-to)356-364
Number of pages9
JournalCritical care medicine
Volume27
Issue number2
DOIs
StatePublished - 1999

Keywords

  • Intestine
  • Nitric oxide
  • Nitric oxide synthase
  • Platelet-activating factor
  • Shock
  • Small intestine

ASJC Scopus subject areas

  • Critical Care and Intensive Care Medicine

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