The role of nitric oxide in tissue destruction.
Nitric oxide (NO) is synthesized via the oxidation of arginine by a family of nitric oxide synthases (NOS), which are either constitutive (ie. endothelial (ec)NOS and neuronal (nc)NOS) or inducible (iNOS). The production of nitric oxide plays a vital role in the regulation of physiological processes, host defence, inflammation and immunity. Pro-inflammatory effects include vasodilation, oedema, cytotoxicity and the mediation of cytokine-dependent processes that can lead to tissue destruction. Nitric oxide-dependent tissue injury has been implicated in a variety of rheumatic diseases, including systemic lupus erythematosus (SLE), rheumatoid arthritis and osteoarthritis. Conversely, the production of NO by endothelial cell NOS may serve a protective, or anti-inflammatory, function by preventing the adhesion and release of oxidants by activated neutrophils in the microvasculature. In this chapter we describe the multifaceted role of nitric oxide in inflammation and address the potential therapeutic implications of NOS inhibition.
Abramson
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SB
Hospital for Joint Diseases/New York University School of Medicine, 301 East 17th Street, New York, NY 10003, USA.
Amin
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Clancy
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RM
Attur
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D000818:Animals; D000893:Anti-Inflammatory Agents / Q000627:therapeutic use; D001172:Arthritis, Rheumatoid / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D002358:Cartilage, Articular / Q000378:metabolism / Q000473:pathology; D006801:Humans; D007249:Inflammation / Q000378:metabolism* / Q000473:pathology; D007596:Joints / Q000378:metabolism / Q000473:pathology; D008180:Lupus Erythematosus, Systemic / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D009569:Nitric Oxide / Q000096:biosynthesis*; D019001:Nitric Oxide Synthase / Q000378:metabolism; D010003:Osteoarthritis / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology
D000893:Anti-Inflammatory Agents; D009569:Nitric Oxide; D019001:Nitric Oxide Synthase