Mechanisms for histamine H1 receptor-mediated vasodilation in isolated canine lingual arteries

Histamine and selective histamine receptor subtype agonists' effects on isolated and perfused canine lingual arteries were investigated with the cannula insertion method. In preparations preconstricted with phenylephrine, histamine and a selective histamine H1 receptor agonist, 2-pyridylethylamine induced a biphasic vascular response in a dose-related manner, i.e., vasoconstriction followed by vasodilatation. The biphasic responses to histamine and 2-pyridylethylamine were inhibited by diphenhydramine, a selective histamine H1 receptor antagonist, but were not influenced by cimetidine, a selective histamine H2 receptor antagonist. Dimaprit, a selective histamine H2 receptor agonist, induced only a slight vasoconstriction which was not modified by cimetidine. Dimaprit never induced vasodilation even at a large dose. A histamine H3 receptor agonist, R-alpha-methylhistamine, did not produce any significant vascular responses. Moreover, histamine-induced vasodilation was in part inhibited by removal of the endothelium, and the vasodilation remaining was abolished by H1 blockade. Thus, it is concluded that in canine lingual arteries there are abundant histamine H1 receptors which mediate both vasoconstriction and vasodilation, and that the histamine-induced vasodilation is in part due to endothelium-dependent mechanisms.