Chiba S, Tsukada M
Department of Pharmacology, Shinshu University School of Medicine, Matsumoto, Nagano, Japan.
Eur J Pharmacol. 1997 Jun 18;329(1):63-8. doi: 10.1016/s0014-2999(97)10105-4.
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.
采用插管法研究了组胺及选择性组胺受体亚型激动剂对离体灌注犬舌动脉的作用。在用去氧肾上腺素预收缩的标本中，组胺和选择性组胺H1受体激动剂2-吡啶乙胺以剂量相关的方式诱导双相血管反应，即先血管收缩后血管舒张。组胺和2-吡啶乙胺的双相反应被选择性组胺H1受体拮抗剂苯海拉明抑制，但不受选择性组胺H2受体拮抗剂西咪替丁的影响。选择性组胺H2受体激动剂二甲双胍仅诱导轻微的血管收缩，西咪替丁对此无影响。即使大剂量使用，二甲双胍也从未诱导血管舒张。组胺H3受体激动剂R-α-甲基组胺未产生任何明显的血管反应。此外，组胺诱导的血管舒张部分被去除内皮所抑制，剩余的血管舒张被H1受体阻断所消除。因此，得出结论：在犬舌动脉中存在丰富的组胺H1受体，其介导血管收缩和血管舒张，且组胺诱导的血管舒张部分归因于内皮依赖性机制。
