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.
- Endothelium-dependent vasodilation
- Endothelium-derived hyperpolarizing factor
- Endothelium-derived relaxing factor
- Histamine H receptor
- Rat mesenteric artery
ASJC Scopus subject areas
- Pharmaceutical Science