Inhaled nitric oxide modulates leukocyte kinetics in the mesenteric venules of endotoxemic rats

OBJECTIVE:to determine whether inhaled nitric oxide (NO) would alter leukocyte kinetics in the septic microvasculature. DESIGN:Randomized, controlled trial. SETTING:Experimental laboratory. SUBJECTS:Male Sprague Dawley rats. INTERVENTIONS:Rats were treated with either saline or endotoxin (10 mg/kg, iv) and then allowed to breathe either air or air plus NO (10 ppm). MEASUREMENTS AND MAIN RESULTS:After a 4-hr period, rolling, firm adhesion, and emigration of leukocytes and endothelial dysfunction were monitored in mesenteric venules by using intravital videomicroscopy. Compared with controls, endotoxemic rats exhibited a profound influx in mesenteric venule rolling leukocytes (55 ± 17 vs. 70 ± 19 leukocytes/min; p < .05), associated with a reduction of leukocyte rolling velocity (83 ± 14 vs. 34 ± 3 μm/sec; p < .05). In endotoxemic rats, venular endothelium leukocyte firm adhesion (1.15 ± 0.32 vs. 4.08 ± 0.96 leukocytes/100 μm; p < .05) and emigration (0.84 ± 0.47 vs. 4.23 ± 1.2 leukocytes/100 μm; p < .05) increased compared with controls. Inhaled NO had no effect on leukocyte kinetics in control rats. Inhaled NO significantly attenuated endotoxin-induced venular endothelium leukocyte adhesion (4.08 ± 0.96 vs. 1.86 ± 0.76 leukocytes/100 μm; p < .05) and emigration (4.23 ± 1.2 vs. 1.68 ± 0.72 leukocytes/100 μm; p < .05). Compared with control rats, macromolecular (FITC-dextran) vascular leakage, expressed as the perivenular/intravenular fluorescence intensity ratio, increased in endotoxemic rats (0.56 ± 0.02 vs. 0.81 ± 0.05; p < .01). Endotoxin-induced macromolecular vascular leakage increases were partially prevented by inhaled NO (0.66 ± 0.01 vs. 0.56 ± 0.02; p < .05). CONCLUSION:These observations suggest that inhaled NO reduces leukocyte adhesion and the degree of vascular permeability dysfunction in mesenteric venule of endotoxemic rats.