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-(−)-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 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 H2 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 mM) significantly inhibited α-methylhistamine-induced endothelium-dependent vasodilation. These findings suggest that α-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.
