Inhaled nitric oxide prevents lung neutrophil accumulation and
pulmonary endothelial dysfunction after mesenteric ischemia
-reperfusion.
Fullerton, David A, John H Eisenach, Robert C McIntyre, Jr., Randall S
Friese, Brett C Sheridan, Gates B Roe, Jeanette Agrafojo, Anirban
Banerjee, Alden H Harken.
The University of Colorado Health Sciences Center, Denver, CO
APStracts 3:0060L, 1996.
This study examined the effect of inhaled nitric oxide (NO) on lung
neutrophil accumulation and endothelial-dependent and -independent
cGMP-mediated mechanisms of pulmonary vasorelaxation following
mesenteric ischemia/reperfusion (I/R) in mechanically ventilated
rats. Inhaled NO (20ppm) was administered in two protocols: (a)
throughout mesenteric I/R and (b) during mesenteric reperfusion
alone. Concentration-response curves were generated (10-9 to 10-6M)
for acetylcholine (ACh), A23187 and sodium nitroprusside (SNP) in
isolated pulmonary arterial rings preconstricted with phenylephrine.
Lung neutrophil accumulation (myeloperoxidase assay, MPO) was
significantly increased from 2.4+/-0.2 units/gm lung wt in controls
to 10.3+/- 0.4 following 1 hr of superior mesenteric artery occlusion
and 2 hrs of reperfusion. Lung MPO activity was not different from
controls in rats receiving inhaled NO either (a) during mesenteric
ischemia and reperfusion or (b) during mesenteric reperfusion alone.
The concentration-response curves demonstrated significant impairment
of pulmonary vasorelaxation by endothelial-dependent mechanisms
(response to ACh and A23187) but not endothelial-independent
pulmonary vasorelaxation (response to SNP) following mesenteric I/R.
This pulmonary vasomotor dysfunction was prevented by administration
of inhaled NO during either mesenteric ischemia and reperfusion or
during mesenteric reperfusion alone. We conclude that inhaled NO
prevents lung neutrophil accumulation and pulmonary vascular
endothelial dysfunction following mesenteric I/R.
Received 8 December 1995; accepted in final form 12 April 1996.
APS Manuscript Number L358-5.
Article publication pending Am. J. Physiol. (Lung Cell. Mol.
Physiology).
ISSN 1080-4757 Copyright 1996 The American Physiological Society.
Published in APStracts on 8 May 96