The role of angiotensin II in postischemic leukocyte‐endothelial interactions

Abstract

Vascular inflammation and enhanced production of angiotensin II (Ang II) are involved in the pathogenesis of hypertension and diabetes, disease states that predispose the afflicted individuals to ischemic disorders. Based on these observations, we postulated that Ang II may play a role promoting leukocyte endothelial interactions (LEI) in postcapillary venules after exposure of the small intestine to ischemia/reperfusion (I/R). Using an intravital microscopy approach in C57Bl/6 mice, we showed that pharmacologic inhibition of angiotensin converting enzyme (ACE) by captopril administration effectively abolished the increases in LEI induced by 45 min of ischemia (superior mesenteric artery occlusion) and 60 min of reperfusion. The postischemic increase in LEI was also attenuated by valsartan, an Ang II AT1 receptor antagonist. Similarly, treatment with the Ang II AT2 receptor blocker PD123,319 limited postischemic LEI. Our work suggests Ang II plays an important role in postischemic leukosequestration, effects that are mediated by both AT1 or AT2 receptors. These studies suggest that ACE inhibition and Ang II receptor antagonists may be useful in the treatment of the inflammatory responses in disorders characterized by I/R. Supported by NIH grant DK 43785.