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

Paul Kubes, Elaine Sihota, Michael J. Hickey

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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
Issue number3 36-3
Publication statusPublished - 1 Sep 1997
Externally publishedYes


  • Inducible nitric oxide synthase
  • Inflammation
  • Microvasculature
  • Selectin

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