Identification and specific blockade of two receptors for histamine in the cardiovascular system.
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.
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D002049:Burimamide / Q000494:pharmacology; D004285:Dogs; D005260:Female; D006339:Heart Rate / Q000187:drug effects; D006439:Hemodynamics / Q000187:drug effects*; D006632:Histamine / Q000494:pharmacology / Q000502:physiology*; D066298:In Vitro Techniques; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects; D009132:Muscles / Q000187:drug effects; D009200:Myocardial Contraction / Q000187:drug effects; D011738:Pyrilamine / Q000494:pharmacology; D011955:Receptors, Drug / Q000187:drug effects*; D012501:Saphenous Vein / Q000187:drug effects; D013270:Stomach / Q000187:drug effects; D014666:Vasomotor System / Q000187:drug effects
D011955:Receptors, Drug; D006632:Histamine; D011738:Pyrilamine; D002049:Burimamide