R-(-)-α-methylhistamine, a histamine H3 receptor agonist, induces endothelium-dependent vasodilation in rat mesenteric resistance arteries

Pengyuan Sun, Xin Jin, Toshihiro Koyama, Simin Li, Yoshihisa Kitamura, Hiromu Kawasaki

Research output: Contribution to journalArticle

14 Citations (Scopus)

Abstract

A novel histamine receptor subtype, histamine H3 receptor, mediates inhibition of peripheral autonomic neurotransmission. The present study was designed to examine vascular effects of histamine H3 receptor by using a selective histamine H3 receptor agonist, R-(-)- a 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 μM methoxamine. In preparations with intact endothelium, perfusion of α-methylhistamine (1-100 μM) 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 H3 receptor antagonists, thioperamide and clobenpropit, but not by chlorpheniramine (histamine H1 receptor antagonist) and cimetidine (histamine H 2 receptor antagonist). Nω-nitro-L-arginine methyl ester (L-NAME, nitric oxide (NO) synthase inhibitor), indomethacin (cyclooxygenase inhibitor) and tetraethylammonium (nonselective K +-channel blocker) and high KCl (30mM) significantly inhibited α-methylhistamine-induced endothelium-dependent vasodilation. These findings suggest that a-methylhistamine induces endothelium-dependent vasodilation mainly via endothelium histamine H3 receptors. It is also suggested that activation of histamine H3 receptors in the endothelium releases mainly NO and partially prostaglandin I2 and endothelium-derived hyperpolarizing factors to induce endothelium-dependent vasodilation.

Original languageEnglish
Pages (from-to)58-63
Number of pages6
JournalBiological and Pharmaceutical Bulletin
Volume33
Issue number1
DOIs
Publication statusPublished - Jan 2010

Fingerprint

Methylhistamines
Histamine Agonists
Mesenteric Arteries
Vasodilation
Endothelium
Histamine H3 Receptors
thioperamide
Perfusion
Blood Vessels
Histamine H3 Antagonists
Histamine H1 Antagonists
Chlorpheniramine
Methoxamine
Histamine Receptors
Tetraethylammonium
Cyclooxygenase Inhibitors
Cimetidine
NG-Nitroarginine Methyl Ester
Epoprostenol
Nitric Oxide Synthase

Keywords

  • Endothelium-dependent vasodilation
  • Endothelium-derived hyperpolarizing factor
  • Endothelium-derived relaxing factor
  • Histamine H receptor
  • Rat mesenteric artery

ASJC Scopus subject areas

  • Pharmaceutical Science
  • Pharmacology

Cite this

R-(-)-α-methylhistamine, a histamine H3 receptor agonist, induces endothelium-dependent vasodilation in rat mesenteric resistance arteries. / Sun, Pengyuan; Jin, Xin; Koyama, Toshihiro; Li, Simin; Kitamura, Yoshihisa; Kawasaki, Hiromu.

In: Biological and Pharmaceutical Bulletin, Vol. 33, No. 1, 01.2010, p. 58-63.

Research output: Contribution to journalArticle

@article{a0406a73ac0f4551b12df326799cf513,
title = "R-(-)-α-methylhistamine, a histamine H3 receptor agonist, induces endothelium-dependent vasodilation in rat mesenteric resistance arteries",
abstract = "A novel histamine receptor subtype, histamine H3 receptor, mediates inhibition of peripheral autonomic neurotransmission. The present study was designed to examine vascular effects of histamine H3 receptor by using a selective histamine H3 receptor agonist, R-(-)- a 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 μM methoxamine. In preparations with intact endothelium, perfusion of α-methylhistamine (1-100 μM) 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 H3 receptor antagonists, thioperamide and clobenpropit, but not by chlorpheniramine (histamine H1 receptor antagonist) and cimetidine (histamine H 2 receptor antagonist). Nω-nitro-L-arginine methyl ester (L-NAME, nitric oxide (NO) synthase inhibitor), indomethacin (cyclooxygenase inhibitor) and tetraethylammonium (nonselective K +-channel blocker) and high KCl (30mM) significantly inhibited α-methylhistamine-induced endothelium-dependent vasodilation. These findings suggest that a-methylhistamine induces endothelium-dependent vasodilation mainly via endothelium histamine H3 receptors. It is also suggested that activation of histamine H3 receptors in the endothelium releases mainly NO and partially prostaglandin I2 and endothelium-derived hyperpolarizing factors to induce endothelium-dependent vasodilation.",
keywords = "Endothelium-dependent vasodilation, Endothelium-derived hyperpolarizing factor, Endothelium-derived relaxing factor, Histamine H receptor, Rat mesenteric artery",
author = "Pengyuan Sun and Xin Jin and Toshihiro Koyama and Simin Li and Yoshihisa Kitamura and Hiromu Kawasaki",
year = "2010",
month = "1",
doi = "10.1248/bpb.33.58",
language = "English",
volume = "33",
pages = "58--63",
journal = "Biological and Pharmaceutical Bulletin",
issn = "0918-6158",
publisher = "Pharmaceutical Society of Japan",
number = "1",

}

TY - JOUR

T1 - R-(-)-α-methylhistamine, a histamine H3 receptor agonist, induces endothelium-dependent vasodilation in rat mesenteric resistance arteries

AU - Sun, Pengyuan

AU - Jin, Xin

AU - Koyama, Toshihiro

AU - Li, Simin

AU - Kitamura, Yoshihisa

AU - Kawasaki, Hiromu

PY - 2010/1

Y1 - 2010/1

N2 - A novel histamine receptor subtype, histamine H3 receptor, mediates inhibition of peripheral autonomic neurotransmission. The present study was designed to examine vascular effects of histamine H3 receptor by using a selective histamine H3 receptor agonist, R-(-)- a 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 μM methoxamine. In preparations with intact endothelium, perfusion of α-methylhistamine (1-100 μM) 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 H3 receptor antagonists, thioperamide and clobenpropit, but not by chlorpheniramine (histamine H1 receptor antagonist) and cimetidine (histamine H 2 receptor antagonist). Nω-nitro-L-arginine methyl ester (L-NAME, nitric oxide (NO) synthase inhibitor), indomethacin (cyclooxygenase inhibitor) and tetraethylammonium (nonselective K +-channel blocker) and high KCl (30mM) significantly inhibited α-methylhistamine-induced endothelium-dependent vasodilation. These findings suggest that a-methylhistamine induces endothelium-dependent vasodilation mainly via endothelium histamine H3 receptors. It is also suggested that activation of histamine H3 receptors in the endothelium releases mainly NO and partially prostaglandin I2 and endothelium-derived hyperpolarizing factors to induce endothelium-dependent vasodilation.

AB - A novel histamine receptor subtype, histamine H3 receptor, mediates inhibition of peripheral autonomic neurotransmission. The present study was designed to examine vascular effects of histamine H3 receptor by using a selective histamine H3 receptor agonist, R-(-)- a 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 μM methoxamine. In preparations with intact endothelium, perfusion of α-methylhistamine (1-100 μM) 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 H3 receptor antagonists, thioperamide and clobenpropit, but not by chlorpheniramine (histamine H1 receptor antagonist) and cimetidine (histamine H 2 receptor antagonist). Nω-nitro-L-arginine methyl ester (L-NAME, nitric oxide (NO) synthase inhibitor), indomethacin (cyclooxygenase inhibitor) and tetraethylammonium (nonselective K +-channel blocker) and high KCl (30mM) significantly inhibited α-methylhistamine-induced endothelium-dependent vasodilation. These findings suggest that a-methylhistamine induces endothelium-dependent vasodilation mainly via endothelium histamine H3 receptors. It is also suggested that activation of histamine H3 receptors in the endothelium releases mainly NO and partially prostaglandin I2 and endothelium-derived hyperpolarizing factors to induce endothelium-dependent vasodilation.

KW - Endothelium-dependent vasodilation

KW - Endothelium-derived hyperpolarizing factor

KW - Endothelium-derived relaxing factor

KW - Histamine H receptor

KW - Rat mesenteric artery

UR - http://www.scopus.com/inward/record.url?scp=75149135250&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=75149135250&partnerID=8YFLogxK

U2 - 10.1248/bpb.33.58

DO - 10.1248/bpb.33.58

M3 - Article

C2 - 20045936

AN - SCOPUS:75149135250

VL - 33

SP - 58

EP - 63

JO - Biological and Pharmaceutical Bulletin

JF - Biological and Pharmaceutical Bulletin

SN - 0918-6158

IS - 1

ER -