A critical role for nitric oxide in intestinal barrier function and
dysfunction.
Alican, Inci, and Paul Kubes.
Department of Medical Physiology, University of Calgary, Calgary,
Alberta, T2N 4N1
APStracts 2:0224G, 1995.
There is growing evidence that endogenous nitric oxide (NO) regulates
mucosal barrier integrity under physiologic conditions and counters
the increase in mucosal permeability associated with acute
pathophysiologic states. The potential mechanisms of action for NO's
protective effect are discussed. These include maintenance of blood
flow, inhibition of platelet and leukocyte adhesion and/or
aggregation within the vasculature, modulation of mast cell
reactivity and scavenging reactive oxygen metabolites such as
superoxide. Based on the data presented, we conclude that both cNOS
-derived endogenous NO and exogenous nitric oxide (NO donors) appear
to reduce the sequelae of acute inflammation. The second section of
this review summarizes the data germaine to prolonged (chronic)
inflammatory conditions associated with the over-production of NO
from the inducible form of NOS (iNOS). Some emphasis is placed on the
role of NO in sepsis and inflammatory bowel disease (IBD) and data to
suggest that NO, or more specifically NO-derived mediators, are
involved in these disorders are summarized. These studies are
compared to recent publications suggesting that inhibition of NO
synthesis with non-specific inhibitors of NOS or selective iNOS
inhibitors may not protect in models of sepsis or IBD. Overall, the
review highlights the potential importance of the type of NOS enzyme
involved in the particular inflammatory process being studied.
Received 8 August 1995; accepted in final form 18 October 1995.
APS Manuscript Number G344-5.
Article publication pending Am. J. Physiol. (Gastrointest. Liver
Physiology).
ISSN 1080-4757 Copyright 1995 The American Physiological Society.
Published in APStracts on 6 November 95