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The FASEB Journal, Vol 9, 1319-1330, Copyright © 1995 by The Federation of American Societies for Experimental Biology

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Molecular mechanisms and therapeutic strategies related to nitric oxide

S Moncada and EA Higgs
Cruciform Project, London, United Kingdom.

The formation of nitric oxide (NO) from L-arginine is now recognized as a ubiquitous biochemical pathway involved in the regulation of the cardiovascular, central, and peripheral nervous systems, as well as in other homeostatic mechanisms. The L-arginine:NO pathway comprises a substrate, L-arginine, a family of enzymes, the NO synthases, and at least one physiological effector system, the soluble guanylate cyclase. NO also inhibits enzymes in target cells and can interact with oxygen- derived radicals to produce other toxic substances. Thus, NO also plays a role in immunological host defense and in the pathophysiology of certain clinical conditions. Several steps in the L-arginine:NO pathway are amenable to manipulation. Some substances will change the concentration and/or actions of NO with consequences that, in certain cases, may be therapeutic. In addition, other agents themselves generate NO and thus mimic the actions of the endogenous mediator. This brief overview will discuss some possible interventions in the pathway and the potential benefits as well as undesirable side effects that might arise from them.


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