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Research ArticleArticle

Neurogenic Vasodilatation of Canine Isolated Small Labial Arteries

Tomio Okamura, Kazuhide Ayajiki, Masami Uchiyama, Masami Uehara and Noboru Toda
Journal of Pharmacology and Experimental Therapeutics March 1999, 288 (3) 1031-1036;
Tomio Okamura
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Kazuhide Ayajiki
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Masami Uchiyama
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Masami Uehara
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Noboru Toda
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Abstract

Mechanisms underlying vasodilatation to nerve stimulation by electrical pulses and nicotine were analyzed in isolated canine small labial arteries. Transmural electrical stimulation (5 and 20 Hz) produced a contraction followed by a relaxation in labial arterial strips denuded of the endothelium, partially contracted with prostaglandin F2α. The contraction was abolished by prazosin or combined treatment with α, β-methylene ATP. In the treated strips, neurogenic relaxation was abolished byNG-nitro-l-arginine (l-NA), a nitric oxide (NO) synthase inhibitor, and restored by l-arginine. The d-enantiomers were without effect. Nicotine (10−4M) also relaxed the arteries, in which the contractile response was abolished by prazosin and α,β-methylene ATP. The relaxant response was attenuated but not abolished by l-NA; the inhibition was reversed by l-arginine. The remaining relaxation by nicotine was abolished by calcitonin gene-related peptide (CGRP)-[8 to 37], a CGRP1 receptor antagonist. Relaxations elicited by a lower concentration of nicotine (2 × 10−5M) sufficient to produce similar magnitudes of response to those induced by 5-Hz electrical nerve stimulation were also inhibited partially by l-NA. Histochemical study with the NADPH-diaphorase method demonstrated positively stained nerve fibers and bundles in the arterial wall, suggesting the presence of neuronal NO synthase. It is concluded that the relaxation induced by electrical nerve stimulation of small labial arteries is mediated exclusively by NO synthesized from l-arginine in nerve terminals, whereas nicotine in the concentrations used evokes relaxations by a mediation of nerve-derived NO and also CGRP, possibly from sensory nerves. The reason why nicotine but not electrical pulses stimulates sensory nerves and elicits vasorelaxation remains unsolved.

Footnotes

  • Send reprint requests to: Noboru Toda, Department of Pharmacology, Shiga University of Medical Science, Seta, Ohtsu 520-2192, Japan. E-mail:toda{at}belle.shiga-med.ac.jp

  • Abbreviations:
    NO
    nitric oxide
    CGRP
    calcitonin gene-related peptide
    PG
    prostaglandin
    l-NA
    NG-nitro-l-arginine
    • Received June 1, 1998.
    • Accepted October 13, 1998.
  • The American Society for Pharmacology and Experimental Therapeutics
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Journal of Pharmacology and Experimental Therapeutics: 288 (3)
Journal of Pharmacology and Experimental Therapeutics
Vol. 288, Issue 3
1 Mar 1999
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Research ArticleArticle

Neurogenic Vasodilatation of Canine Isolated Small Labial Arteries

Tomio Okamura, Kazuhide Ayajiki, Masami Uchiyama, Masami Uehara and Noboru Toda
Journal of Pharmacology and Experimental Therapeutics March 1, 1999, 288 (3) 1031-1036;

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Research ArticleArticle

Neurogenic Vasodilatation of Canine Isolated Small Labial Arteries

Tomio Okamura, Kazuhide Ayajiki, Masami Uchiyama, Masami Uehara and Noboru Toda
Journal of Pharmacology and Experimental Therapeutics March 1, 1999, 288 (3) 1031-1036;
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