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1 Department of Molecular and Cellular Physiology, Louisiana State University Medical Center, Shreveport, Louisiana 71130; and 2 Radiation Biology Branch, National Cancer Institute, Bethesda, Maryland 20892
The role of nitric oxide (NO) in inflammation
represents one of the most studied yet controversial subjects in
physiology. A number of reports have demonstrated that NO
possesses potent anti-inflammatory properties, whereas an equally
impressive number of studies suggest that NO may promote
inflammation-induced cell and tissue dysfunction. The reasons
for these apparent paradoxical observations are not entirely clear;
however, we propose that understanding the physiological chemistry
of NO and its metabolites will provide a blueprint by which
one may distinguish the regulatory/anti-inflammatory properties of NO from its deleterious/proinflammatory
effects. The physiological chemistry of NO is
complex and encompasses numerous potential reactions. In an attempt to
simplify the understanding of this chemistry, the
physiological aspects of NO chemistry may be categorized into direct
and indirect effects. This type of classification allows for
consideration of timing, location, and rate of production of
NO and the relevant targets likely to be affected. Direct
effects are those reactions in which NO interacts directly
with a biological molecule or target and are thought to occur under
normal physiological conditions when the rates of NO production are
low. Generally, these types of reactions may serve regulatory
and/or anti-inflammatory functions. Indirect effects, on
the other hand, are those reactions mediated by NO-derived intermediates such as reactive nitrogen oxide species derived from
the reaction of NO with oxygen or superoxide and are produced when
fluxes of NO are enhanced. We postulate that these types of reactions
may predominate during times of active inflammation. Consideration of
the physiological chemistry of NO and its metabolites will hopefully
allow one to identify which of the many NO-dependent reactions are
important in modulating the inflammatory response and may help in the
design of new therapeutic strategies for the treatment of inflammatory
tissue injury.
arthritis; colitis; leukocytes; free radicals; superoxide; cancer
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