R-(-)-.ALPHA.-Methylhistamine, a Histamine H3 Receptor Agonist, Induces Endothelium-Dependent Vasodilation in Rat Mesenteric Resistance Arteries

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Author(s)

    • Sun Pengyuan Sun Pengyuan
    • Department of Clinical Pharmaceutical Sciences, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
    • Jin Xin Jin Xin
    • Department of Clinical Pharmaceutical Sciences, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
    • Li Simin
    • Department of Clinical Pharmaceutical Sciences, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
    • Kitamura Yoshihisa
    • Department of Pharmaceutical Care and Health Science, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
    • Kawasaki Hiromu
    • Department of Clinical Pharmaceutical Sciences, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University

Abstract

A novel histamine receptor subtype, histamine H<sub>3</sub> receptor, mediates inhibition of peripheral autonomic neurotransmission. The present study was designed to examine vascular effects of histamine H<sub>3</sub> receptor by using a selective histamine H<sub>3</sub> receptor agonist, <i>R</i>-(−)-α methylhistamine (α-methylhistamine), in rat mesenteric resistance arteries. The isolated mesenteric vascular beds were perfused with Krebs solution and perfusion pressure was measured. Active tone was produced by perfusion of Krebs solution containing 7 μ<small>M</small> methoxamine. In preparations with intact endothelium, perfusion of α-methylhistamine (1—100 μ<small>M</small>) for 1 min produced a concentration-dependent vasodilation. The maximum vasodilation at the highest concentration was approximately 45%. This vasodilation was abolished by endothelium removal and attenuated by histamine H<sub>3</sub> receptor antagonists, thioperamide and clobenpropit, but not by chlorpheniramine (histamine H<sub>1</sub> receptor antagonist) and cimetidine (histamine H<sub>2</sub> receptor antagonist). <i>N</i><sup>ω</sup>-nitro-<small>L</small>-arginine methyl ester (<small>L</small>-NAME, nitric oxide (NO) synthase inhibitor), indomethacin (cyclooxygenase inhibitor) and tetraethylammonium (nonselective K<sup>+</sup>-channel blocker) and high KCl (30 m<small>M</small>) significantly inhibited α-methylhistamine-induced endothelium-dependent vasodilation. These findings suggest that α-methylhistamine induces endothelium-dependent vasodilation mainly <i>via</i> endothelium histamine H<sub>3</sub> receptors. It is also suggested that activation of histamine H<sub>3</sub> receptors in the endothelium releases mainly NO and partially prostaglandin I<sub>2</sub> and endothelium-derived hyperpolarizing factors to induce endothelium-dependent vasodilation.

Journal

  • Biological and Pharmaceutical Bulletin

    Biological and Pharmaceutical Bulletin 33(1), 58-63, 2010

    The Pharmaceutical Society of Japan

Cited by:  1

Codes

  • NII Article ID (NAID)
    130000140192
  • NII NACSIS-CAT ID (NCID)
    AA10885497
  • Text Lang
    ENG
  • Article Type
    Journal Article
  • ISSN
    0918-6158
  • NDL Article ID
    10497330
  • NDL Source Classification
    ZS51(科学技術--薬学)
  • NDL Call No.
    Z53-V41
  • Data Source
    CJPref  NDL  J-STAGE 
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