NITRIC OXIDE AND NITROGEN OXIDES

Abstract

Nitric oxide (NO) is a ubiquitous signaling molecule with a variety of biological functions. Due to its unstable nature, NO is subject to many chemical reactions, which depend on its biological environment and which may be involved in its effects. NO is generated via the oxidation of l -arginine catalyzed by different isotypes of the enzyme NO synthase (NOS), including neuronal NOS (nNOS), inducible NOS (iNOS), and endothelial NOS (eNOS), which are all present in the respiratory tract. Relatively small amounts of NO generated from the constitutive isoforms (nNOS and eNOS) as well as S-nitrosothiols are primarily involved in the regulation of airway and vascular smooth muscle tone, employing both cyclic GMP-dependent and independent pathways. In addition to its effects on smooth muscle tone, large amounts of NO produced by iNOS may have proinflammatory and cytotoxic effects involved in the host defense against microorganisms and malignant cells. Most of these effects may be attributed to the formation of the highly reactive oxidant species peroxynitrite (ONOO − ), produced under oxidative stress conditions during the inflammatory response. The bioavailability of l -arginine to NOS is under important control of arginase, by competition for the common substrate. Induction of arginase during inflammatory reactions may cause a relative deficiency of NO, resulting in reduced inhibition of airway and vascular tone and in production of oxygen radicals by iNOS, which enhances ONOO − formation. Aberrant NO homeostasis is involved in a number of pulmonary diseases, including asthma, COPD, cystic fibrosis, and pulmonary hypertension, which may be monitored by measurement of NO in the exhaled air. Inhalation of NO may be of benefit for the improvement of hemodynamics in pulmonary hypertension.