AJP - Lung Cellular and Molecular Physiology, Vol 269, Issue 1 2-L5, Copyright © 1995 by American Physiological Society
Inhaled nitric oxide prevents neutrophil-mediated, oxygen radical-dependent leak in isolated rat lungs
D. M. Guidot, M. J. Repine, B. M. Hybertson and J. E. Repine
Webb-Waring Institute for Biomedical Research, University of Colorado Health Sciences Center, Denver 82062, USA.
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.
