Reactive oxygen species mediate angiotensin II-induced leukocyte-endothelial cell interactions in vivo

J Leukoc Biol. 2001 Aug;70(2):199-206.

Abstract

Chronically elevated angiotensin II (Ang-II)-induced hypertension is partly mediated by superoxide production. In this study, we have investigated whether the leukocyte-endothelial cell interactions elicited by Ang-II involve reactive oxygen species (ROS) generation. Intravital microscopy within the rat mesenteric microvessels was used. Superfusion (60 min) with Ang-II (1 nM) induced significant increases in leukocyte rolling flux, adhesion, and emigration, which were inhibited by pretreatment with superoxide dismutase or catalase. Dihydrorhodamine-123 oxidation indicated that ROS are primarily produced by the vessel wall. Administration of dimethylthiourea, desferrioxamine, or N-acetylcysteine provoked significant reductions in Ang-II-induced leukocyte-endothelial cell interactions. In addition, a blockade of platelet-activating factor or leukotrienes also attenuated such responses significantly. The results presented indicate that in vivo Ang-II-induced leukocyte recruitment is dependent on the generation of intra- and extracellular ROS. Therefore, the use of anti-oxidants might constitute an alternative therapy for the control of the subendothelial leukocyte infiltration associated with hypertension and atherosclerosis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Angiotensin II / pharmacology*
  • Animals
  • Catalase / pharmacology
  • Cell Adhesion
  • Cell Communication / drug effects
  • Chemotaxis, Leukocyte / drug effects
  • Endothelium, Vascular / cytology*
  • Kinetics
  • Leukocytes / cytology*
  • Leukocytes / physiology
  • Leukotriene Antagonists
  • Leukotrienes / physiology
  • Male
  • Microcirculation
  • Microscopy, Video
  • Platelet Activating Factor / antagonists & inhibitors
  • Platelet Activating Factor / physiology
  • Rats
  • Rats, Sprague-Dawley
  • Reactive Oxygen Species / physiology*
  • Splanchnic Circulation
  • Superoxide Dismutase / pharmacology

Substances

  • Leukotriene Antagonists
  • Leukotrienes
  • Platelet Activating Factor
  • Reactive Oxygen Species
  • Angiotensin II
  • Catalase
  • Superoxide Dismutase