The role of nitric oxide in hypoxia-induced colonic dysfunction in
the neonatal rat.
Brown, James F., and Barry L. Tepperman.
Department of Physiology, Faculty of Medicine, University of
Western Ontario, London, Ontario, Canada, N6A5C1
APStracts 3:0221G, 1996.
As well as being an important mediator in the regulation of intestinal
integrity, nitric oxide, when produced in large quantities by the
inducible isoform of nitric oxide synthase can also be cytotoxic. The
aim of this study was to examine the role of nitric oxide in hypoxia
induced colonic injury in neonatal rats. Rats (10-12 days old) were
exposed to a hypoxic environment of 14%O2/86%N2 for 30?min. Nitric
oxide synthase activity in colonic tissue was measured via the
conversion of [14C]-L-arginine to [14C]-L-citrulline. Epithelial
permeability was assessed by measuring the plasma to lumen flux of
3H-mannitol or the luminal protein content of colonic lavage. The
role of neutrophils was assessed by pretreatment with anti-neutrophil
serum (200?[mu]l/kg I.P.) and measurement of tissue myeloperoxidase
activity. Hypoxia resulted in an elevation in the activity of the
inducible Ca2+-independent isoform of nitric oxide synthase in
colonic tissue, which was maximal between 4?h and 6?h post hypoxia
and was associated with an increase in myeloperoxidase activity, 3H
-mannitol flux, luminal protein content, and histological damage.
These effects were attenuated by pretreatment with dexamethasone or
the NO synthase inhibitors aminoguanidine and L-NAME, whereas the
inactive stereoisomer D-NAME was without effect. Pretreatment with
antineutrophil serum significantly reduced circulating neutrophils,
myeloperoxidase activity and Ca2+-independent nitric oxide synthase
activity. These findings demonstrate that hypoxia induced colonic
injury in neonatal rats is associated with elevated nitric oxide
synthase activity which is related to an increase in neutrophil
infiltration.
Received 23 April 1996; accepted in final form 30 September 1996.
APS Manuscript Number G148-6.
Article publication pending Am. J. Physiol. (Gastrointest. Liver
Physiology).
ISSN 1080-4757 Copyright 1996 The American Physiological Society.
Published in APStracts on 5 November 1996