Nitric oxide donor decreases neutrophil adhesion in both lung and peritoneum during peritonitis.
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.


METHODS
In experiment 1, rats (n = 12) were given saline or 10 micrograms/kg of SNAP intravenously followed by continuous infusion of saline, or of 2, 20, or 200 micrograms/kg/h SNAP until sacrifice. Ten minutes after injection of saline or SNAP, 10(7) Escherichia coli were injected into the peritoneal cavity. Five hours after challenge, 10(6) fluorescein-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 micrograms/kg of SNAP intravenously and infused with saline or 20 micrograms/kg/h SNAP; E. coli was 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 micrograms/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.


CONCLUSIONS
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.
Fukatsu
K
K
Department of Surgery, University of Tokyo, Japan.
Saito
H
H
Han
I
I
Furukawa
S
S
Lin
M T
MT
Matsuda
T
T
Ikeda
S
S
Inoue
T
T
Yasuhara
H
H
Muto
T
T
D000818:Animals; D001784:Blood Gas Analysis; D002448:Cell Adhesion / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D006439:Hemodynamics / Q000187:drug effects; D007668:Kidney / Q000378:metabolism; D007958:Leukocyte Count; D008099:Liver / Q000378:metabolism; D008168:Lung / Q000378:metabolism*; D008297:Male; D008856:Microscopy, Fluorescence; D009504:Neutrophils / Q000378:metabolism*; D009569:Nitric Oxide / Q000378:metabolism*; D010396:Penicillamine / Q000031:analogs & derivatives* / Q000494:pharmacology; D010537:Peritoneum / Q000378:metabolism*; D010538:Peritonitis / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley
C110881:S-nitro-N-acetylpenicillamine; D009569:Nitric Oxide; D010396:Penicillamine