Nitric Oxide and Other Vasoactive Agents

Publisher Summary Nitric oxide (NO) is a gas radical that is enzymatically produced by the oxidation and cleavage of one of the terminal nitrogen atoms of the amino acid L-arginine. The reaction is dependent on electrons donated by the cofactor NADPH, requires oxygen, and yields L-citrulline as a coproduct. Nitric oxide is involved in a variety of physiological and pathophysiological processes including vasodilatation, neurotransmission, and the killing of various pathogens and in the genesis of inflammatory diseases. These broad-ranging actions of NO are determined largely by the site of NO synthesis, the rate of NO synthesis, and how much is generated and by the nature of the environment into which it is released. The reactivity of NO is influenced in particular by the presence of reactive oxygen intermediates and the activity of anti-oxidant defense systems. A family of three related enzymes, the NO synthases (NOS), regulates the synthesis of NO. These are characterized as a neuronal form (type 1; nNOS) originally isolated from brain, an endothelial form (type 3; eNOS) originally isolated from bovine aortic endothelial cells, and an inducible form (type 2; iNOS) originally isolated from murine macrophages. The predominant NOS isoforms expressed by bone tissues are eNOS and iNOS, both of which are present in osteoblasts, osteocytes, and osteoclasts. Synthesis of NO by these cells is stimulated by a variety of signals including hormones, cytokines, and mechanical loading resulting in number of distinct physiological and pathophysiogical responses.