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Nitric Oxide and Endothelial Dysfunction

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Studies on Pediatric Disorders

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Abstract

Sun Tzu taught in The Art of War “If you know the enemy and know yourself, you need not fear the result of a hundred battles.” When it is necessary to understand cardiovascular and cerebrovascular diseases, atherosclerosis, chronic kidney diseases, and so on, it is important to know the normophysiology and pathophysiology of endothelial function. The development of oxidative stress in the earlier-mentioned diseases has long been suggested to relate to the balance of nitric oxide (NO) levels. The molecular structure of endothelial NO synthase (eNOS) has now been elucidated; eNOS consists of a C-terminal reductase domain and an N-terminal oxygenase domain and is homo-dimerized through a Cys99-Cys94 motif on each monomer with the coordination of zinc. Cys99 is the key residue that also participates in the binding of tetrahydrobiopterin (BH4) and L-arginine to produce NO. When these factors are lacking, the enzyme can uncouple to produce superoxide. In this short review, selected key topics essential to understanding the biologic significance of NO and eNOS are discussed.

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Abbreviations

ADMA:

Asymmetrical dimethyl arginine

ADP:

Adenosine diphosphate

AMP:

Adenosine monophosphate

ARE/EpRE:

Antioxidant/electrophile-responsive element

ATP:

Adenosine triphosphate

BH4:

Tetrahydrobiopterin

CKD:

Chronic kidney disease

COX-2:

Cyclooxygenase-2

Cys:

Cysteine

DDAH1:

Dimethylarginine dimethylaminohydrolase-1

eNOS:

Endothelial NO synthase

ESRD:

End-stage renal disease

GMP:

Guanosine monophosphate

GTP:

Guanosine triphosphate

L-FABP:

L-type fatty acid-binding protein

L-NAME:

Ng-nitro-l-arginine methyl

L-NMMA:

Ng-monomethyl-L-arginine

5-MTHF:

5-Methyltetrahydrofolate

5-MTHFR:

5, 10-Methylenetetrahydrofolate reductase

NADPH:

Nicotinamide adenine dinucleotide phosphate

8-nitro-cGMP:

8-Nitroguanosine 3′ 5′-cyclic monophosphate

NO:

Nitric oxide

NOS:

Nitric oxide synthase

NOX:

Nicotinamide adenine dinucleotide phosphate oxidase

OA-NO2 :

Nitro fatty acids

15d-PGJ2 :

15-Deoxy-∆12,14-prostaglandin J2

RNOS:

Reactive nitrogen oxide species

SNO-hemoglobin:

S-nitrosohemoglobin

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Authors and Affiliations

  1. Nephrology and Endocrinology, Hemodialysis and Apheresis, The University of Tokyo Hospital, Tokyo, Japan

    Eisei Noiri M.D., Ph.D.

  2. The International Center for Materials Nanoarchitectonics (MANA), National Institute for Materials Science (NIMS), Ibaraki, Japan

    Kousuke Minami Ph.D.

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  1. Eisei Noiri M.D., Ph.D.
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Correspondence to Eisei Noiri M.D., Ph.D. .

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Editors and Affiliations

  1. Dentistry and Pharmaceutical Sciences Department of Pediatrics, Okayama University Graduate School of Medicine, Okayama, Japan

    Hirokazu Tsukahara

  2. Department of Pediatrics, Kansai Medical University, Osaka, Japan

    Kazunari Kaneko

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Noiri, E., Minami, K. (2014). Nitric Oxide and Endothelial Dysfunction. In: Tsukahara, H., Kaneko, K. (eds) Studies on Pediatric Disorders. Oxidative Stress in Applied Basic Research and Clinical Practice. Springer, New York, NY. https://doi.org/10.1007/978-1-4939-0679-6_4

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