Nitric Oxide Donor Decreases Neutrophil Adhesion in both Lung and Peritoneum during Peritonitis

Abstract

Background.As nitric oxide (NO) is an antiadhesive molecule, exogenous NO may modulate neutrophil adhesion in organs. This study was designed to examine the effects of the NO donor SNAP (S-nitroso-acetyl penicillamine) on neutrophil adhesion at the inflammatory site and in remote organs, in peritonitis using a fluorescent microscopic method.Materials and methods.In experiment 1, rats (n= 12) were given saline or 10 μg/kg of SNAP intravenously followed by continuous infusion of saline, or of 2, 20, or 200 μg/kg/h SNAP until sacrifice. Ten minutes after injection of saline or SNAP, 107Escherichia coliwere injected into the peritoneal cavity. Five hours after challenge, 106fluorescein-labeled neutrophils were infused. Peritoneal samples, lungs, liver, and kidney were harvested for counting of labeled neutrophils under epifluorescent microscopy. In experiment 2, rats (n= 25) were treated with saline or 10 μg/kg of SNAP intravenously and infused with saline or 20 μg/kg/h SNAP;E. coliwas injected as in experiment 1. Before or 5 h after challenge, hemodynamic data were obtained. Then, labeled neutrophils were infused for counting of neutrophil numbers in organs. Arterial blood gas data and the circulating neutrophil number were also determined.Results: Experiment 1.Twenty and 200 μg/kg/h SNAP infusions tended to reduce labeled neutrophil numbers in lungs, while all three SNAP doses decreased the peritoneal labeled neutrophil numbers.Results: Experiment 2.Five hours after bacterial injection, SNAP infusion simultaneously decreased both pulmonary and peritoneal labeled neutrophil numbers. SNAP had no effect on hemodynamic and blood gas data, or on circulating neutrophil numbers.Conclusion.NO donors may be useful for preventing neutrophil-associated lung injury, but should be used with caution in light of the possible adverse effects on host defense in the peritoneal cavity.