title: Nitric oxide inhibition decreases neutrophil adhesion at the inflammatory site, while increasing adhesion in remote organs in peritonitis.
abstract: Nitric oxide (NO) is a regulator of leukocyte adhesion in the microcirculation. This study was designed to examine the effects of a NO synthase inhibitor on neutrophil adhesion in the peritoneum, lung, liver, and kidney in a rat peritonitis model using a fluorescence microscopic method. Sprague-Dawley rats were given normal saline (control) or N omega-nitro-L-arginine methyl ester (L-NAME) at dosages of 10 mg/kg (N10) or 100 mg/kg (N100) (n = 66) intraperitoneally. One hour after pretreatment fluorescein-labeled neutrophils were infused without bacterial challenge (0 hr). Other rats received an injection of 10(7) Escherichia coli into the peritoneal cavity 1 hr after pretreatment. Labeled neutrophils were infused 1 and 5 hr after bacterial challenge. Just 2 min after neutrophil injection, blood samples were obtained and the animals were killed. Five peritoneal samples (omentum, mesentery, parietal peritoneum, colon, and ileum), both lungs, the liver, and the right kidney were harvested for counting of labeled neutrophils under epifluorescent microscopy. Combined plasma nitrite/nitrate levels were determined. In another set of rats (n = 36), an arterial catheter was inserted after L-NAME treatment and bacterial challenge. At 0, 1, 5, and 12 hr after challenge, blood pressure, heart rate, and arterial blood gas data were measured. One hour after E. coli challenge, the number of neutrophils in the peritoneum was significantly lower in both L-NAME-treated groups than in the control group. In contrast, the number of labeled neutrophils in the lungs was significantly higher in the N100 group than in the control group. Neutrophil accumulation in the lungs and peritoneum at 0 and 5 hr and in the liver and kidney at 0, 1, and 5 hr did not differ among groups, nor did combined plasma nitrite/nitrate levels. L-NAME treatment had no influence on either hemodynamic or blood gas data. In conclusion, administration of L-NAME increases neutrophil adhesion in the lung, while decreasing that in the peritoneum. NO plays an important role in neutrophil adhesion at the inflammatory site, as well as in remote organs, during peritonitis. NO inhibition may be detrimental, due to neutrophil sequestration, in this peritonitis model.
authors.affiliation: Department of Surgery, University of Tokyo, Japan.
authors.forename: K
authors.initials: K
authors.lastname: Fukatsu
authors.forename: H
authors.initials: H
authors.lastname: Saito
authors.forename: I
authors.initials: I
authors.lastname: Han
authors.forename: S
authors.initials: S
authors.lastname: Furukawa
authors.forename: Y
authors.initials: Y
authors.lastname: Hashiguchi
authors.forename: M T
authors.initials: MT
authors.lastname: Lin
authors.forename: T
authors.initials: T
authors.lastname: Matsuda
authors.forename: T
authors.initials: T
authors.lastname: Inaba
authors.forename: T
authors.initials: T
authors.lastname: Inoue
authors.forename: S
authors.initials: S
authors.lastname: Ikeda
authors.forename: H
authors.initials: H
authors.lastname: Yasuhara
authors.forename: T
authors.initials: T
authors.lastname: Muto
mesh_terms: D000818:Animals; D001784:Blood Gas Analysis; D002448:Cell Adhesion; D004791:Enzyme Inhibitors / Q000008:administration & dosage / Q000494:pharmacology*; D004927:Escherichia coli Infections / Q000209:etiology / Q000378:metabolism*; D006439:Hemodynamics; D007668:Kidney / Q000378:metabolism; D007958:Leukocyte Count / Q000187:drug effects; D008099:Liver / Q000378:metabolism; D008168:Lung / Q000378:metabolism; D008297:Male; D019331:NG-Nitroarginine Methyl Ester / Q000008:administration & dosage / Q000494:pharmacology*; D009504:Neutrophils / Q000378:metabolism*; D009569:Nitric Oxide / Q000037:antagonists & inhibitors*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D010537:Peritoneum / Q000378:metabolism*; D010538:Peritonitis / Q000378:metabolism* / Q000382:microbiology; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D004791:Enzyme Inhibitors; D009569:Nitric Oxide; D019001:Nitric Oxide Synthase; D019331:NG-Nitroarginine Methyl Ester