Role of Nitric Oxide in Leukocyte-Endothelial Interaction in Cerebral Venules during Reperfusion after Global Ischemia

Kim, Sae Han; Lee, Young Bae; Jung, Ju Ho

Abstract

OBJECTIVE
Reactive oxygen metabolites and polymorphonuclear leukocytes have been implicated in the pathophysiology of reperfusion injury. The mechanisms involved in superoxide-mediated leukocyte adherence remain unclear, however, nitric oxide(NO) may contribute to this response. The present study is undertaken to elucidate mechamisms controlling NO based mechanisms that regulated leukocyte-endothelial interactions in the cerebral vasculature after global cerebral ischemia and reperfusion. METHODS: Pial venular leukocyte adherence of anesthetized newborn piglets was quantified by in situ fluorescence videomicroscopy through closed cranial windows during basal conditions and during 2hours of reperfusion after global ischemia induced by 9minutes of asphyxia. Nitric oxide synthase(NOS) was inhibited by local window superfusion of L-nitroarginine(NA); superfusion of sodium nitroprusside(SNP) was used to donate NO. RESULTS: The mean number of adherent leukocytes to cerebral venules in the 9minutes asphyxia and 2hours reperfusion group were 161+/-19 compared with 13+/-4 in the nonasphyxial group. Superfusion of L-NA through the cranial window for 2hours resulted in leukocyte adherence similar to that observed during the initial 2hours of reperfusion after asphyxia. Leukocyte adherence was not additionally increased in asphyxic animal treated with L-NA. SNP inhibited asphyxia induced leukocyte adherence back to control levels. CONCLUSIONS: Nitric oxide inhibits leukocyte adherence to cerebral venules during the initial hours of reperfusion after asphyxia, and that NO supplementation inhibit asphyxia induced leukocyte adherence back to control levels. These results indicate that NO is an important factor in ischemia-reperfusion induced leukocyte adherence.