Interaction between reactive oxygen species and nitric oxide in the microvascular response to systemic hypoxia. hypoxia results in oxidative stress due to a change in the reactive oxygen species (ROS)-nitric oxide (NO) balance. These experiments explored two mechanisms for the altered ROS-NO balance: 1) decreased NO synthesis by NO synthase due to limited O 2 substrate availability and 2) increased superoxide generation. ROS levels and leukocyte adherence in mesenteric venules of rats during

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... oxia were studied in the absence and presence of an NO donor [spermine NONOate (SNO)] and of the NO precursor L-arginine. We hypothesized that if the lower NO levels during hypoxia were due to O 2 substrate limitation, L-arginine would not prevent hypoxia-induced microvascular responses. Graded hypoxia (produced by breathing 15, 10, and 7.5% O 2) increased both ROS (123 Ϯ 6, 148 Ϯ 11, and 167 Ϯ 3% of control) and leukocyte adherence. ROS levels during breathing of 10 and 7.5% O 2 were significantly attenuated by SNO (105 Ϯ 6 and 108 Ϯ 3%, respectively) and L-arginine (117 Ϯ 5 and 115 Ϯ 2%, respectively). Both interventions reduced leukocyte adherence by similar degrees. The fact that the effects of Larginine were similar to those of SNO does not support the idea that NO generation is impaired in hypoxia and suggests that tissue NO levels are depleted by the increased ROS during hypoxia. mesenteric venules; leukocyte adherence; superoxide; dihydrorhodamine ALTHOUGH CONSIDERABLE EFFORT has been made to define microvascular responses to ischemia/reperfusion (5, 13), relatively little information exists regarding the effect of systemic hypoxia, i.e., a reduction in blood oxygen (O 2 ) levels without an interruption in flow. Results from in vitro systems have shown that a reduction in PO 2 of the perfusate increases leukocyte adherence to cultured endothelial cells (2, 21) and to umbilical vein segments (4, 22). However, opposing results have also been obtained, as decreased adhesive interactions between granulocytes and human umbilical vein endothelial cells were observed during hypoxia (24). Recent in vivo studies have demonstrated micro-