IDENTIFICATION AND SPECIFIC BLOCKADE OF 2 RECEPTORS FOR HISTAMINE IN CARDIOVASCULAR-SYSTEM

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  • 1 January 1976
    • journal article
    • research article
    • Vol. 196  (1) , 1-14
Abstract
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 burimamide 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 vasodilataion which was blocked by metiamide and mepyramine, respectively. Constriction of the saphenous vein produced by histamine involved interaction with H1-receptors only. In the intact dog histamine increased heart rate and decreased left ventricular cardiac contractility (dp/dt; the rate of rise of peak ventricular pressure) 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. Both peripheral vascular and cardiac responses to histamine are mediated through activation of H1-receptors.