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Recent advances in research on nitrergic nerve-mediated vasodilatation

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Abstract

Cerebral vascular resistance and blood flow were widely considered to be regulated solely by tonic innervation of vasoconstrictor adrenergic nerves. However, pieces of evidence suggesting that parasympathetic nitrergic nerve activation elicits vasodilatation in dog and monkey cerebral arteries were found in 1990. Nitric oxide (NO) as a neurotransmitter liberated from parasympathetic postganglionic neurons decreases cerebral vascular tone and resistance and increases cerebral blood flow, which overcome vasoconstrictor responses to norepinephrine liberated from adrenergic nerves. Functional roles of nitrergic vasodilator nerves are found also in peripheral vasculature, including pulmonary, renal, mesenteric, hepatic, ocular, uterine, nasal, skeletal muscle, and cutaneous arteries and veins; however, adrenergic nerve-induced vasoconstriction is evidently greater than nitrergic vasodilatation in these vasculatures. In coronary arteries, neurogenic NO-mediated vasodilatation is not clearly noted; however, vasodilatation is induced by norepinephrine released from adrenergic nerves that activates β1-adrenoceptors. Impaired actions of NO liberated from the endothelium and nitrergic neurons are suggested to participate in cerebral hypoperfusion, leading to brain dysfunction, like that in Alzheimer’s disease. Nitrergic neural dysfunction participates in impaired circulation in peripheral organs and tissues and also in systemic blood pressure increase. NO and vasodilator peptides, as sensory neuromediators, are involved in neurogenic vasodilatation in the skin. Functioning of nitrergic vasodilator nerves is evidenced not only in a variety of mammals, including humans and monkeys, but also in non-mammals. The present review article includes recent advances in research on the functional importance of nitrergic nerves concerning the control of cerebral blood flow, as well as other regions, and vascular resistance. Although information is still insufficient, the nitrergic nerve histology and function in vasculatures of non-mammals are also summarized.

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Abbreviations

ADMA:

Asymmetric dimethylarginine

CGRP:

Calcitonin gene-related peptide

eNOS:

Endothelial NOS

5-HT:

5-Hydroxytryptamine

l-NA:

N G-nitro-l-arginine

NADPH:

Reduced nicotinamide adenine dinucleotide phosphate

l-NAME:

l-NA methylester

7-NI:

7-Nitroindazole

l-NMMA:

N G-monomethyl-l-arginine

nNOS:

Neuronal NOS

NO:

Nitric oxide

NOS:

Nitric oxide synthase

PIN:

Protein inhibitor of nNOS

l-SMTC:

S-methyl-l-thiocitrulline

SHR:

Spontaneously hypertensive rats

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Acknowledgments

This work was supported in part by grant-in-aid for scientific research from the Ministry of Education, Culture, Sport, Science and Technology of Japan (23390055).

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The authors have no conflict of interest in any matter related to this work.

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  1. Toyama Institute for Cardiovascular Pharmacology Research, 7-13, 1-Cho-me, Azuchi-machi, Chuo-ku, Osaka, 541-0052, Japan

    Noboru Toda

  2. Department of Pharmacology, Shiga University of Medical Science, Seta, Otsu, 520-2192, Japan

    Noboru Toda & Tomio Okamura

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  1. Noboru Toda
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Toda, N., Okamura, T. Recent advances in research on nitrergic nerve-mediated vasodilatation. Pflugers Arch - Eur J Physiol 467, 1165–1178 (2015). https://doi.org/10.1007/s00424-014-1621-0

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  • DOI: https://doi.org/10.1007/s00424-014-1621-0

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