Nitric Oxide Formation in the Vascular Wall: Regulation and Functional Implications

  • R. Busse
  • I. Fleming
  • V. B. Schini
Part of the Current Topics in Microbiology and Immunology book series (CT MICROBIOLOGY, volume 196)

Abstract

Numerous investigations have indicated that in both health and disease the shortlived radical nitric oxide (NO) is a key effector in the vascular system (Fig. 1). NO is generated by a five-electron oxidation of one of the terminal guanidino nitrogen atoms of l-arginine, catalyzed by NO synthases, and reaches the surrounding target cells by simple diffusion. The principal physiological source of NO in the vascular system is the endothelium, which constitutively expresses a NO synthase. The most important functions of endothelium-derived NO are the control of blood flow, and hence the supply of oxygen to organs, and the control of blood cell interaction with the vascular wall. Under certain pathophysiological conditions, endothelial cells are no longer the main source of NO. Indeed, in most types of vascular cells (e.g., vascular smooth muscle cells, macrophages, fibroblasts and endothelial cells) a NO producing pathway is induced following exposure to cytokines, such as interleukin-1β (IL-1β) and tumor necrosis factor-α (TNF-α), the levels of which are elevated in response to infection and injury. NO generated by this pathway in large amounts may account, at least in part, for the cytotoxic effect of macrophages and thus play a crucial role in host defense. The finding that NO can have such contrasting effects, i.e., to be protective and yet also cytotoxic, may be explained by the involvement of two NO-generating systems regulated by distinctly different mechanisms.

Keywords

Adduct Nitrite Interferon NADPH Galle 

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Copyright information

© Springer-Verlag Berlin Heidelberg 1995

Authors and Affiliations

  • R. Busse
    • 1
  • I. Fleming
    • 1
  • V. B. Schini
    • 1
  1. 1.Zentrum der PhysiologieKlinikum der JWG-UniversitätFrankfurt/MainGermany

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