Reactive oxygen species mediate angiotensin II-induced leukocyte-endothelial cell interactions in vivo.
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.
Alvarez
A
A
Department of Pharmacology, Faculty of Medicine, University of Valencia, Spain.
Sanz
M J
MJ
D000804:Angiotensin II / Q000494:pharmacology*; D000818:Animals; D002374:Catalase / Q000494:pharmacology; D002448:Cell Adhesion; D002450:Cell Communication / Q000187:drug effects; D002634:Chemotaxis, Leukocyte / Q000187:drug effects; D004730:Endothelium, Vascular / Q000166:cytology*; D007700:Kinetics; D007962:Leukocytes / Q000166:cytology* / Q000502:physiology; D020024:Leukotriene Antagonists; D015289:Leukotrienes / Q000502:physiology; D008297:Male; D008833:Microcirculation; D018715:Microscopy, Video; D010972:Platelet Activating Factor / Q000037:antagonists & inhibitors / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D017382:Reactive Oxygen Species / Q000502:physiology*; D013152:Splanchnic Circulation; D013482:Superoxide Dismutase / Q000494:pharmacology
D020024:Leukotriene Antagonists; D015289:Leukotrienes; D010972:Platelet Activating Factor; D017382:Reactive Oxygen Species; D000804:Angiotensin II; D002374:Catalase; D013482:Superoxide Dismutase