Abstract
The purpose of this study was to determine if nitric oxide reduces the increased leukocyte-endothelial interactions observed with acute hypoxia in the mesenteric microcirculation. We studied the effects of the NO donor nitrosylated glutathione (GSNO) in a murine model of acute hypoxia. The microcirculation of two groups of Sprague-Dawley rats was observed via intravital microscopy. After 20 minutes of baseline observation, rats received an intravenous bolus of either GSH (n=3) or GSNO (n=3) at a dose of 20μg/kg followed by continuous infusion of 20 μg/kg/hr via external jugular venous catheter. After 10 minutes, rats were then acutely exposed to 30 minutes of 12% oxygen via hood and then returned to 21% oxygen for an additional 60 minutes. Serial video recordings with play back analysis off-line were taken for data recording. Statistical analysis was via two-way repeated measures ANOVA. Exposure to acute hypoxia caused increased rolling and adherence of leukocytes to the post-capillary venule in the GSH group similar to rats exposed to hypoxia, without intravenous administration of GSH(data not shown). However, when compared to the GSH group, the addition of GSNO significantly attenuated leukocyte rolling during and after hypoxic exposure (during hypoxia 96±14.8 vs. 20±14.8 cells/minute; after hypoxia: 88±14.8 vs. 45.4±14.8 cells/minute; mean±SEM; GSH vs. GSNO; p=0.02). Leukocyte adherence in animals treated with GSH increased during and after hypoxic exposure; this increase was inhibitted in animals given GSNO (during hypoxia 4±1 vs. 0.23±1 cells/100μm; after hypoxia: 5.4±1 vs. 0.23±1 cells/100μm; mean ±SEM; GSH vs. GSNO; p=0.003). There was no difference in systemic mean arterial blood pressure (p=.928) or shear stress (p=.14) between the two groups throughout the experiment. We speculate that the increased interaction of leukocytes with the endothelial cell of the post-capillary venule seen during and after acute exposure to hypoxia may be, in part, due to a loss of NO.
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