Endogenous but not exogenous nitric oxide decreases TNF-α-induced leukocyte rolling

Paul Kubes, Elaine Sihota, Michael J. Hickey

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27 Citations (Scopus)

Abstract

Inhibition of nitric oxide (NO) synthesis in mesenteric microvessels increases leukocyte rolling. The objective of this study was to determine whether inducible NO synthase (iNOS) can modulate tumor necrosis factor-α (TNF-α)-induced leukocyte rolling. Leukocyte rolling was examined using intravital microscopy of TNF-α-treated feline mesenteric microvasculature. Leukocyte rolling increased progressively over 3 h of TNF-α treatment. Pretreatment with the selective iNOS inhibitor amino-guanidine further doubled TNF-α-induced leukocyte rolling. Aminoguanidine alone did not affect baseline blood pressure or leukocyte kinetics. However, in the same animals N(G)-nitro-L-arginine methyl ester caused a rapid increase in blood pressure, confirming that constitutive NOS activity persisted in aminoguanidine- treated animals. Furthermore, aminoguanidine did not affect leukocyte rolling in an acute model of leukocyte recruitment (ischemia/reperfusion), suggesting that the exacerbated rolling induced by aminoguanidine with TNF-α as a stimulus was not a nonspecific effect. Addition of the NO donor spermine-NO had no effect on TNF-α-associated leukocyte rolling. These data raise the possibility of a physiological role for the increased production of NO from iNOS, i.e., regulation of leukocyte rolling and potentially the inflammatory response.

Original languageEnglish
Pages (from-to)G628-G635
Number of pages8
JournalAmerican Journal of Physiology: Gastrointestinal and Liver Physiology
Volume273
Issue number3 36-3
DOIs
Publication statusPublished - 1 Sep 1997
Externally publishedYes

Keywords

  • Inducible nitric oxide synthase
  • Inflammation
  • Microvasculature
  • Selectin

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