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 whe ther the leukocyte-endothetial 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 primaril y produced by the vessel wall. Administration of dimethylthiourea, desferri oxamine, or N-acetylcisteine provoked significant reductions in Ang-II-indu ced leukocyte-endothelial cell interactions. In addition, a blockade of pla telet-activating factor or leukotrienes also attenuated such responses sign ificantly. The results presented indicate that in vivo Ang-II-induced leuko cyte recruitment is dependent on the generation of intra- and extracellular ROS. Therefore, the use of anti-oxidants might constitute an alternative t herapy for the control of the subendothelial leukocyte infiltration associa ted with hypertension and atherosclerosis.