Powell J R, Brody M J
J Pharmacol Exp Ther. 1976 Jan;196(1):1-14.
Histamine caused a fall in blood pressure in anesthetized dogs and cats which was only partially attenuated by mepyramine (pyrilamine), a histamine type H1-receptor antagonist. Further treatment with burimide or metiamide, type H2-receptor antagonists, caused nearly complete attenuation of the response to histamine. Burimamide alone had no effect on vasodilatation produced by histamine in the dog gracilis muscle whereas mepyramine alone caused a partial attenuation. An H2-receptor agonist, 4-methylhistamine and an H1-receptor agonist, 2-(2-pyridyl)ethylamine, both produced vasodilatation which was blocked by metiamide and mepyramine, respectively. Constriction of the saphenous vein produced by histamine was found to involve interaction with H1-receptors only. In the intact dog, histamine increased heart rate and decreased left ventricular dp/dt through direct effects. Mepyramine prevented the increase in heart rate but did not affect the chronotropic actions of isoproterenol and glyceryl trinitrate. H1-receptor blockade did not alter inotropic effects whereas subsequent H2-receptor blockade prevented the negative inotropic effect of histamine. It is concluded that both peripheral vascular and cardiac responses to histamine are mediated through activation of H1- and H2-histamine receptors.
组胺可使麻醉犬和猫的血压下降，而组胺H1受体拮抗剂美吡拉敏（新安替根）只能部分减弱这一作用。用H2受体拮抗剂丁咪胺或甲硫咪胺进一步处理后，对组胺的反应几乎完全减弱。单独使用丁咪胺对组胺在犬股薄肌中引起的血管舒张没有影响，而单独使用美吡拉敏则可使其部分减弱。H2受体激动剂4-甲基组胺和H1受体激动剂2-（2-吡啶基）乙胺均引起血管舒张，分别被甲硫咪胺和美吡拉敏阻断。发现组胺引起的隐静脉收缩仅涉及与H1受体的相互作用。在完整的犬中，组胺通过直接作用使心率加快，左心室dp/dt降低。美吡拉敏可防止心率加快，但不影响异丙肾上腺素和硝酸甘油的变时作用。H1受体阻断不改变心肌收缩力，而随后的H2受体阻断可防止组胺的负性肌力作用。结论是，组胺对外周血管和心脏的反应均通过组胺H1和H2受体的激活介导。
