Inhaled nitric oxide prevents neutrophil mediated, oxygen radical
dependent leak in isolated rat lungs.
Guidot, David M., Michael J. Repine, Brooks M. Hybertson, John E.
Repine.
Webb-Waring Institute for Biomedical Research and the Division of
Pulmonary/Critical Care Medicine, University of Colorado Health
Sciences Center, Denver, CO
APStracts 2:0030L, 1995.
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 FMLP
(10-7M) and human neutrophils (1300/ul). 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 mm Hg to 11.7+/-0.5 mm Hg at 10 min, lungs
perfused with FMLP and neutrophils in which PAP was maintained at 7
mm Hg 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 at 30
min 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.
Received 2 November 1994; accepted in final form 16 February
1995.
APS Manuscript Number L317-4.
Article publication pending Am. J. Physiol. (Lung Cell. Mol.
Physiology).
ISSN 1080-4757 Copyright 1995 The American Physiological Society.
Published in APStracts on 7 March 1995.