A novel histamine receptor subtype, histamine H
3 receptor, mediates inhibition of peripheral autonomic neurotransmission. The present study was designed to examine vascular effects of histamine H
3 receptor by using a selective histamine H
3 receptor agonist,
R-(−)-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
M methoxamine. In preparations with intact endothelium, perfusion of α-methylhistamine (1—100 μ
M) 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
3 receptor antagonists, thioperamide and clobenpropit, but not by chlorpheniramine (histamine H
1 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 (30 m
M) significantly inhibited α-methylhistamine-induced endothelium-dependent vasodilation. These findings suggest that α-methylhistamine induces endothelium-dependent vasodilation mainly
via endothelium histamine H
3 receptors. It is also suggested that activation of histamine H
3 receptors in the endothelium releases mainly NO and partially prostaglandin I
2 and endothelium-derived hyperpolarizing factors to induce endothelium-dependent vasodilation.
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