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Department of Pharmacology and Therapeutics, University of Calgary, Calgary, Alberta, Canada T2N 4N1
Nitric oxide is a crucial mediator of
gastrointestinal mucosal defense, but, paradoxically, it also
contributes to mucosal injury in several situations. Inhibitors of
nitric oxide synthesis and compounds that release nitric oxide have
been useful pharmacological tools for evaluating the role of nitric
oxide in gastrointestinal physiology and pathophysiology. Newer
inhibitors with selectivity for one of the isoforms of nitric oxide
synthase are even more powerful tools and may have utility as
therapeutic agents. Also, agents that can scavenge nitric oxide or
peroxynitrite are promising as drugs to prevent nitric oxide-associated
tissue injury. Compounds that release nitric oxide in small amounts
over a prolonged period of time may also be very useful for prevention
of gastrointestinal injury associated with shock and with the use of
drugs that have ulcerogenic effects. Indeed, the coupling of a nitric
oxide-releasing moiety to nonsteroidal anti-inflammatory drugs has
proven to be a valid means of substantially reducing the
gastrointestinal toxicity of these drugs without decreasing their efficacy.
inflammation; ulcer; inflammatory bowel disease; ischemia-reperfusion
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