Inhaled nitric oxide prevents neutrophil-mediated, oxygen radical-dependent leak in isolated rat lungs.
We found that ventilation with nitric oxide (NO, 50 ppm) significantly (P < 0.05) reduced capillary leak (as reflected by weight gain and Ficoll retention) in isolated rat lungs perfused for 60 min with N-formyl-methionyl-leucyl-phenylalanine (fMLP; 10(-7) M) and human neutrophils (1,300/microliters). Perfusion with previously heated neutrophils (48 degrees C for 10 min, which inactivates NADPH oxidase) did not cause weight gain or Ficoll retention, indicating that neutrophil-derived oxidants mediated lung leak. Although perfusion with fMLP and neutrophils increased mean pulmonary artery pressures (PAP) from 7 to 11.7 +/- 0.5 mmHg at 10 min, lungs perfused with fMLP and neutrophils in which PAP was maintained at 7 mmHg by reducing perfusion flow rates also developed significant (P < 0.05) weight gain and Ficoll retention. Furthermore, inhaled NO did not reduce (P > 0.05) PAP at 10 min and only modestly reduced PAP at 30 and 60 min of perfusion. Our results suggest that oxidative endothelial damage, and not increased hydrostatic pressure, was the primary cause of the capillary leak, and that the protection provided by inhaled NO was not solely a consequence of vasodilation. We conclude that inhaled NO prevents neutrophil-mediated, oxygen radical-dependent leak in isolated rat lungs, and speculate that inhaled NO has anti-inflammatory properties in addition to its ability to cause pulmonary vasodilation.
Guidot
D M
DM
Webb-Waring Institute for Biomedical Research, University of Colorado Health Sciences Center, Denver 82062, USA.
Repine
M J
MJ
Hybertson
B M
BM
Repine
J E
JE
D000280:Administration, Inhalation; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D002199:Capillary Permeability / Q000187:drug effects; D006801:Humans; D066298:In Vitro Techniques; D008168:Lung / Q000378:metabolism*; D008297:Male; D009240:N-Formylmethionine Leucyl-Phenylalanine / Q000494:pharmacology; D009504:Neutrophils / Q000187:drug effects / Q000502:physiology*; D009569:Nitric Oxide / Q000494:pharmacology*; D010477:Perfusion; D011651:Pulmonary Artery / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D017382:Reactive Oxygen Species / Q000378:metabolism*
D017382:Reactive Oxygen Species; D009569:Nitric Oxide; D009240:N-Formylmethionine Leucyl-Phenylalanine