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‐acetylcisteine 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 vivoAng‐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.