Nitric oxide decreases lung injury following intestinal
ischemia.
Terada, Lance S., Nancy N. Mahr, Eugene D. Jacobson.
University of Colorado Health Sciences Center, Box C322, 4200 E.
Ninth Ave., Denver, CO 80262
APStracts 3:0404A, 1996.
Following injury to a primary organ, mediators are released into the
circulation and may initiate inflammation of remote organs. We
hypothesized that the local production of nitric oxide (NO) may act
to limit the spread of inflammation to secondarily targeted organs.
In anesthetized rats, 30 min intestinal ischemia followed by 2 h
reperfusion (I/R) did not increase lung albumin leak. However,
following treatment with NG-nitro-L-arginine methyl ester (L-NAME),
intestinal I/R led to increased lung leak, suggesting a protective
effect of endogenous NO. The site of action of NO appeared to be the
lung and not the gut, because 1) following treatment with L-NAME,
local delivery of NO to the lung by inhalation abolished the increase
in intestinal I/R-induced lung leak; 2) L-NAME had no effect on
epithelial permeability (51Cr-EDTA clearance) of reperfused small
bowel; and 3) following treatment with L-NAME, local delivery of NO
to the gut by luminal perfusion did not improve epithelial
permeability of reperfused intestines. Further, L-NAME increased and
inhaled NO decreased the density of lung neutrophils in rats
subjected to intestinal I/R, and treatment with the selectin
antagonist fucoidan abolished L-NAME-induced lung leak in rats
subjected to intestinal I/R. We conclude that endogenous lung NO
limits secondary lung injury following intestinal I/R by decreasing
pulmonary neutrophil retention.
Received 4 June 1996; accepted in final form 26 July 1996.
APS Manuscript Number A515-6.
Article publication pending Journal of Applied Physiology.
ISSN 1080-4757 Copyright 1996 The American Physiological Society.
Published in APStracts on 19 September 1996