Blocking of endogenous nitric oxide increases white blood cell accumulation in rat lung.
OBJECTIVE
Nitric oxide (NO) is a known selective dilator of the pulmonary vascular tree. There also is evidence that it plays a role in diminishing neutrophil adherence to vascular endothelial cells. An understanding of these effects of NO on the pulmonary microcirculation is essential to our understanding of its mechanisms of action as well as its potential as a therapeutic agent to reduce neutrophil sequestration and subsequent lung injury and inflammation from a variety of conditions. This study examines the direct effects of inhibition of endogenous NO synthesis with the L-arginine analog, Nomega-nitro-L-arginine methyl ester (L-NAME) on neutrophil accumulation within the lung.


METHODS
Lung samples from 2 groups of rats (n = 14 for each study group) were studied. One group was given an intravenous infusion of L-NAME, and the other received normal saline (NS), at 2 mg/kg/min for 1 hour. The accumulation of neutrophils within the lungs was assessed quantitatively by myeloperoxidase (MPO) assay as well as by microscopic examination by a pathologist blinded to the 2 groups.


RESULTS
The L-NAME group showed increased MPO activity in the lung compared with the NS group (mean MPO/mean bicinchoninic acid [BCA]: 43.46 +/- 3.10 U/microg v 23.58 +/- 2.48 U/microg; mean MPO/g wet lung [gwl]: 57.60 +/- 5.98 U/gwl v 27.10 +/- 3.84 U/gwl, mean +/- SEM; P <.05). Histologic examination (n = 6 each group) showed 26 +/- 2 neutrophils/5 hpf for the L-NAME group versus 18 +/- 1 neutrophils/5 hpf for the NS group (P < 0.05).


CONCLUSIONS
These data indicate that the inhibition of endogenous NO has a direct effect of increasing neutrophil sequestration in the pulmonary vasculature and alveoli. This suggests that endogenous NO plays a critical role in the control of neutrophil-endothelial cell interactions in the lung.
Roman
Angela
A
Division of Pediatric Surgery, Department of Surgery, University of Virginia Health System, Charlottesville, VA 22908-0709, USA.
Legallo
Robin
R
McGahren
Eugene D
ED
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000494:pharmacology; D008168:Lung / Q000098:blood supply / Q000276:immunology*; D008297:Male; D008833:Microcirculation / Q000187:drug effects / Q000276:immunology; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009504:Neutrophils / Q000187:drug effects* / Q000502:physiology; D009569:Nitric Oxide / Q000037:antagonists & inhibitors* / Q000096:biosynthesis; D009195:Peroxidase / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley
D004791:Enzyme Inhibitors; D009569:Nitric Oxide; D009195:Peroxidase; D019331:NG-Nitroarginine Methyl Ester