ABSTRACT
This chapter attempts to examine the therapeutics of nitric oxide (NO) modulation from a system perspective. Therapeutic efficacy of NO modulators is considered not only from the traditional pharmacological viewpoints of potency and enzyme specificity, but also from those of absorption, metabolism and biodistribution, and pharmacokinetics. These properties jointly contribute to the overall therapeutic efficacy, safety, and selectivity of any drug, and therefore must be taken into consideration if useful NO modulators are to be developed for therapeutic use in the future. Two approaches have been used to enhance NO availability in NO-deficient diseases. The first approach is to augment NO production endogenously by supplying l-arginine, which is metabolically converted by nitric oxide synthase (NOS) to NO and citrulline. The second approach is to administer NO donors, which release NO either spontaneously or via enzymatic reactions. These latter agents liberate NO independent of NOS activity and therefore mediate their actions regardless of the functional state of NOS.
