Microvascular oxidative stress preceding leukocyte activation elicited by in vivo nitric oxide suppression

M. Suematsu, T. Tamatani, F. A. Delano, M. Miyasaka, M. Forrest, H. Suzuki, G. W. Schmid-Schonbein

Research output: Contribution to journalArticle

117 Citations (Scopus)

Abstract

This study was aimed to determine the mechanism by which endogenous nitric oxide suppression promotes leukocyte adhesion in vivo. The rat mesenteric microcirculation was superfused with N(G)-nitro-L-arginine methyl ester (L- NAME; 100 μM), and intracellular oxidant formation in several microcirculatory cellular components such as arteriolar and venular endothelium and mast cells was visually monitored by digital microfluorography assisted by carboxydichlorofluorescein (CDCF), a hydroperoxide-sensitive fluorogenic probe. Adherent leukocyte density was measured simultaneously. L-NAME induced a significant time-dependent increase in CDCF fluorescence in arteriolar and venular endothelium and mast cells followed by firm adhesion of leukocytes. L-NAME-induced CDCF elevation showed a different spatial distribution compared with that evoked by N- formylmethionyl-leucyl-phenylalanine, in which only local venular segments with adhering leukocytes exhibited CDCF fluorescence enhancement. The level of hydroperoxide formation in arterioles and venules evoked by 60-min L-NAME superfusion was equivalent to that induced by the superfusion of ~880 μM tert-butyl hydroperoxide for 10 min. Pretreatment with anti-intracellular adhesion molecule-1, anti-P-selectin, or anti-CD18 monoclonal antibody attenuated L-NAME-elicited venular leukocyte adhesion without abolishing CDCF fluorescence in situ. Pretreatment with desferioxamine (50 mg/kg iv; 1 h before L-NAME superfusion) significantly diminished the iron-catalyzed hydroperoxide formation in arterioles and venules, but not in interstitial mast cells, as well as subsequent venular leukocyte adhesion. These findings indicate that endogenous nitric oxide may modulate oxidative stress in mast cells, arteriolar and venular microvascular endothelium and thereby can play a crucial role in leukocyte recruitment in venules.

Original languageEnglish
Pages (from-to)H2410-H2415
JournalAmerican Journal of Physiology - Heart and Circulatory Physiology
Volume266
Issue number6 35-6
DOIs
Publication statusPublished - 1994

Keywords

  • P-selectin
  • endothelium-leukocyte interaction
  • intracellular adhesion molecule-1
  • iron
  • mast cells
  • oxygen free radicals

ASJC Scopus subject areas

  • Physiology
  • Cardiology and Cardiovascular Medicine
  • Physiology (medical)

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