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Nitric Oxide Synthase Inhibitors and Cerebral Vasospasm

  • Conference paper
Early Brain Injury or Cerebral Vasospasm

Part of the book series: Acta Neurochirurgica Supplements ((NEUROCHIRURGICA,volume 110/1))

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Abstract

l-arginine is a source of nitric oxide (NO) that is cleaved from the terminal guanidino nitrogen atom by nitric oxide synthase (NOS). NO evokes, because of its free radical properties and affinity to heme, ferrous iron and cysteine, a wide spectrum of physiological and pathophysiological effects. For many years, different exogenous NOS inhibitors were used to elucidate the role of NOS and NO in health and disease. Later, endogenous NOS inhibitors, as asymmetric dimethylarginine (ADMA) were discovered. Endogenous inhibitors as ADMA are produced by post-translational methylation of l-arginine which is catalyzed by a family of protein N-methyltransferases (PRMT), using S-adenosylmethionine as a methyl group donor. ADMA is eliminated by dimethylarginine dimethylaminohydrolases (DDAH I or II). ADMA hydrolysis increases NOS activity and NO production. Furthermore, l-citrulline, a by-product of ADMA hydrolysis as well as of NO production by NOS, can in turn inhibit DDAH. Therefore, endogenous inhibition of NOS can be modified via different ways (1) changing the availability of l-arginine and/or of l-citrulline; (2) stimulating or inhibiting DDAH activity; (3) modifying methylation via regulating availability of adenosylmethionine; or (4) modifying PRMT activity. Research elucidating the role of NOS inhibitors in respect of delayed cerebral vasospasm after subarachnoid hemorrhage is summarized.

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Authors and Affiliations

  1. Department of Neurosurgery, Ruprecht-Karls-University Heidelberg, Im Neuenheimer Feld 400, 69120, Heidelberg, Germany

    C. S. Jung

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  1. C. S. Jung
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Correspondence to C. S. Jung .

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Editors and Affiliations

  1. Department of Neurosurgery, Southwest Hospital, Third Military Medical University, Gaotanyan 30, Chongqing, 400038, China

    H.-J. Steiger  & Hua Feng  & 

  2. Department of Neurosurgery, Huashan Hospital, Fudan University, Shanghai, China

    Ying Mao

  3. Departments of Physiology and Neurosurgery, Loma Linda University School of Medicine, Risley Hall, Room 223, 92354, Loma Linda, California, USA

    John H. Zhang

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Jung, C.S. (2011). Nitric Oxide Synthase Inhibitors and Cerebral Vasospasm. In: Feng, H., Mao, Y., Zhang, J.H. (eds) Early Brain Injury or Cerebral Vasospasm. Acta Neurochirurgica Supplements, vol 110/1. Springer, Vienna. https://doi.org/10.1007/978-3-7091-0353-1_16

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  • DOI: https://doi.org/10.1007/978-3-7091-0353-1_16

  • Publisher Name: Springer, Vienna

  • Print ISBN: 978-3-7091-0352-4

  • Online ISBN: 978-3-7091-0353-1

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