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Review ArticleReview Article

Cerebral Blood Flow Regulation by Nitric Oxide: Recent Advances

Noboru Toda, Kazuhide Ayajiki and Tomio Okamura
Pharmacological Reviews March 2009, 61 (1) 62-97; DOI: https://doi.org/10.1124/pr.108.000547
Noboru Toda
Toyama Institute for Cardiovascular Pharmacology Research, Osaka, Japan (N.T.); and Department of Pharmacology, Shiga University of Medical Science, Shiga, Japan (N.T., K.A., T.O.)
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Kazuhide Ayajiki
Toyama Institute for Cardiovascular Pharmacology Research, Osaka, Japan (N.T.); and Department of Pharmacology, Shiga University of Medical Science, Shiga, Japan (N.T., K.A., T.O.)
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Tomio Okamura
Toyama Institute for Cardiovascular Pharmacology Research, Osaka, Japan (N.T.); and Department of Pharmacology, Shiga University of Medical Science, Shiga, Japan (N.T., K.A., T.O.)
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Abstract

Nitric oxide (NO) is undoubtedly quite an important intercellular messenger in cerebral and peripheral hemodynamics. This molecule, formed by constitutive isomers of NO synthase, endothelial nitric-oxide synthase, and neuronal nitric-oxide synthase, plays pivotal roles in the regulation of cerebral blood flow and cell viability and in the protection of nerve cells or fibers against pathogenic factors associated with cerebral ischemia, trauma, and hemorrhage. Cerebral blood flow is increased and cerebral vascular resistance is decreased by NO derived from endothelial cells, autonomic nitrergic nerves, or brain neurons under resting and stimulated conditions. Somatosensory stimulation also evokes cerebral vasodilatation mediated by neurogenic NO. Oxygen and carbon dioxide alter cerebral blood flow and vascular tone mainly via constitutively formed NO. Endothelial dysfunction impairs cerebral hemodynamics by reducing the bioavailability of NO and increasing the production of reactive oxygen species (ROS). The NO-ROS interaction is an important issue in discussing blood flow and cell viability in the brain. Recent studies on brain circulation provide quite useful information concerning the physiological roles of NO produced by constitutive isoforms of nitric-oxide synthase and how NO may promote cerebral pathogenesis under certain conditions, including cerebral ischemia/stroke, cerebral vasospasm after subarachnoid hemorrhage, and brain injury. This information would contribute to better understanding of cerebral hemodynamic regulation and its dysfunction and to development of novel therapeutic measures to treat diseases of the central nervous system.

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Pharmacological Reviews: 61 (1)
Pharmacological Reviews
Vol. 61, Issue 1
1 Mar 2009
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Review ArticleReview Article

Cerebral Blood Flow Regulation by Nitric Oxide: Recent Advances

Noboru Toda, Kazuhide Ayajiki and Tomio Okamura
Pharmacological Reviews March 1, 2009, 61 (1) 62-97; DOI: https://doi.org/10.1124/pr.108.000547

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Review ArticleReview Article

Cerebral Blood Flow Regulation by Nitric Oxide: Recent Advances

Noboru Toda, Kazuhide Ayajiki and Tomio Okamura
Pharmacological Reviews March 1, 2009, 61 (1) 62-97; DOI: https://doi.org/10.1124/pr.108.000547
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  • Article
    • Abstract
    • I. Introduction
    • II. Synthesis and Actions of Nitric Oxide
    • III. Physiological Control of Cerebral Blood Flow
    • IV. Cerebral Blood Flow Regulation by Nitric Oxide under Pathological Conditions
    • V. Pharmacological Implications of Nitric Oxide and Nitric Oxide-Related Agents for Miscellaneous Brain Diseases
    • VI. Summary and Conclusion
    • Acknowledgments
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