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Nitric oxide (#NO) is a free radical signal transducing agent which acts via reversible binding to transition metals, often the heme-iron moiety of enzymes such as guanylate cyclase. The actions of this molecule have been highly conserved throughout millions of years of evolution, and include: (1) control of vascular hemodynamics via regulation of smooth muscle cell relaxation. (2) participation in host defense mechanisms, by virtue of diverse *NOmediated toxic target molecule reactions. (3) regulation of platelet aggregation and the vascular wall adherence of platelets and neutrophils. (4) service as a central and peripheral neurotransmitter. (5) regulation of smooth muscle proliferation. It is apparent that *NO plays a central role in regulating not only the delivery of oxygen to tissues, but also in the response of tissues to oxidant stress and periods of hypoxia or ischemia.