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Nitric Oxide Synthase Inhibitors: Mechanism of Action and in Vivo Studies

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Biochemical, Pharmacological, and Clinical Aspects of Nitric Oxide

Abstract

Nitric oxide synthase (NOS) catalyzes the NADPH- and O2-dependent oxidation of Larginine to citrulline and nitric oxide (NO) (1,2). At least three distinct isoforms of NOS occur in mammals including a brain isoform (bNOS) that produces NO having a poorly defined role in neurotransmission (3,4), an isoform in vascular endothelial cells (eNOS) that produces NO having a vasodilatory role in normal blood pressure homeostasis (5,7), and an inducible isoform (iNOS) that is expressed in many tissues in response to lipopolysaccharide (LPS) and various cytokines (e.g. tumor necrosis factor (TNF), interleukin-1 (IL-1), interleukin-2 (IL-2) (8). Although iNOS has a physiological role in the control of intracellular pathogens including viruses (9) and may play a role in the cytostatic/cytotoxic reaction of macrophages to tumor cells (10,11), overproduction of NO by iNOS expressed in vascular smooth muscle (VSM) and endothelial cells has been shown to be a major hypotensive mediator in septic and cytokine-induced shock (7,12–15). Recent evidence also suggests iNOS-derived NO accounts in part for the tissue damage seen in inflammatory disorders including arthritis (16–18). Elucidation of these potentially pathological roles of iNOS and speculation that bNOS has a role in the post-ischemic damage of stroke (4) has stimulated efforts to selectively inhibit the NOS isoforms.

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  1. Department of Biochemistry, Medical College of Wisconsin, Milwaukee, WI, 53226, USA

    Owen W. Griffith

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  1. Israel Institute for Biological Research, Ness-Ziona, Israel

    Ben Avi Weissman , Nahum Allon  & Shlomo Shapira ,  & 

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Griffith, O.W. (1995). Nitric Oxide Synthase Inhibitors: Mechanism of Action and in Vivo Studies. In: Weissman, B.A., Allon, N., Shapira, S. (eds) Biochemical, Pharmacological, and Clinical Aspects of Nitric Oxide. Springer, Boston, MA. https://doi.org/10.1007/978-1-4615-1903-4_3

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  • DOI: https://doi.org/10.1007/978-1-4615-1903-4_3

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