Influence of ACE and AT(1)-receptor inhibition on the ischemia/reperfusioninduced leukocyte adherence

Introduction: Enalapril has been shown to attenuate I/R injury. Aim of this study is to characterize the role and possible mechanisms of ACE and AT(1) receptor inhibition in I/R injury. Methods: Using intravital microscopy in a model of a 4 h tourniquet ischemi a in the hamster dorsal skinfold chamber leukocyte endothelium interaction after application of 5 mg/kg Enalapril or Losartan was examined. Furthermor e leukocyte adhesion and ICAM-1/VCAM-1 expression on HUVECs after hypoxial/ reoxygenation was determined. Results: We could demonstrate that ACE inhibiton by enalapril - in contrast to AT(1)-receptor inhibiton - reduced the postischemic leukocyte adhesion. Furthermore Enalapril inhibited the hypoxia induced endothelial ICAM-1 and VCAM-1 expression and leukocyte adherence in a HUVEC model in the absence of Angiotensinogen. Conclusion: Taken together this suggests a pharmacologic effect of Enalapri l on the NF-kappa B regulated neutrophil cytokine and endothelial adhesion molecule expression.