Hypoxia causes leukocyte adherence to mesenteric venules in nonacclimatized, but not in acclimatized, rats

Departments of 1 Molecular and Integrative Physiology and of 2 Pediatrics, University of Kansas Medical Center, Kansas City, Kansas 66160 Although the effects of ischemia-reperfusion have received considerable attention, few studies have directly evaluated the microcirculatory response to systemic hypoxia. The overall objective of this study was to assess the effect of environmental hypoxia on adhesive interactions of circulating leukocytes with rat mesenteric venules by using intravital microscopy. Experiments were designed to 1 ) characterize the adhesive interactions of circulating leukocytes to venules during acute hypoxia produced by a reduction in inspired P O 2 , 2 ) evaluate the role of nitric oxide in these adhesive interactions, 3 ) determine whether the effect of hypoxia on leukocyte adhesive interactions differs between acclimatized and nonacclimatized rats, and 4 ) assess whether compensatory changes in nitric oxide formation contribute to this difference. The results showed that acute hypoxia promotes leukocyte-endothelial adherence in mesenteric venules of nonacclimatized rats. The mechanism of this response is consistent with depletion of nitric oxide within the microcirculation. In contrast, no leukocyte-endothelial adherence occurred during hypoxia in rats acclimatized to hypobaric hypoxia. The results are consistent with increased nitric oxide formation due to expression of inducible nitric oxide synthase during the acclimatization period. Further studies are needed to establish the cause of nitric oxide depletion during acute hypoxia as well as to define the compensatory responses that attenuate hypoxia-induced leukocyte-endothelial adherence in the microvasculature of acclimatized rats. nitric oxide; reactive oxidants; inducible nitric oxide synthase; leukocyte-endothelial adhesive interactions