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

Although the effects of ischemia-reperfusion have received considerable att ention, few studies have directly evaluated the microcirculatory response t o systemic hypoxia. The overall objective of this study was to assess the e ffect of environmental hypoxia on adhesive interactions of circulating leuk ocytes with rat mesenteric venules by using intravital microscopy. Experime nts were designed to 1)characterize the adhesive interactions of circulatin g leukocytes to venules during acute hypoxia produced by a reduction in ins pired Po-2, 2) evaluate the role of nitric oxide in these adhesive interact ions, 3) determine whether the effect of hypoxia on leukocyte adhesive inte ractions differs between acclimatized and nonacclimatized rats, and 4) asse ss whether compensatory changes in nitric oxide formation contribute to thi s difference. The results showed that acute hypoxia promotes leukocyte-endo thelial adherence in mesenteric venules of nonacclimatized rats. The mechan ism of this response is consistent with depletion of nitric oxide within th e microcirculation. In contrast, no leukocyte-endothelial adherence occurre d during hypoxia in rats acclimatized to hypobaric hypoxia. The results are consistent with increased nitric oxide formation due to expression of indu cible nitric oxide synthase during the acclimatization period. Further stud ies are needed to establish the cause of nitric oxide depletion during acut e hypoxia as well as to define the compensatory responses that attenuate hy poxia-induced leukocyte-endothelial adherence in the microvasculature of ac climatized rats.