Different mechanisms of action of histamine in isolated arteries of the dog.

1 In helically-cut strips of dog coronary, superior mesenteric, right gastro-epiploic and renal arteries contracted with prostaglandin F2 alpha (PGF 2 alpha), histamine produced a dose-related relaxation, while, in contrast, the amine caused only a contraction of cerebral arterial strips. 2 The contractile response of cerebral arteries to histamine was attenuated by chlorpheniramine (10(-6)M) but was unaffected by cimetidine (10(-5)M). Relaxant responses to histamine of coronary and renal arteries were significantly attenuated by treatment with cimetidine and to a similar extent by combined treatment with cimetidine and chlorpheniramine. Chlorpheniramine alone was ineffective. 3 In mesenteric and gastro-epiploic arteries, relaxant responses to histamine were attenuated only slightly by cimetidine. Chlorpheniramine slowed the development of histamine-induced relaxations but did not alter the magnitude of the relaxations. Combined treatment with these H1- and H2- antagonists attenuated the histamine-induced relaxations to an appreciably greater extent than treatment with cimetidine alone. 4 It may be concluded that the cerebroarterial contraction induced by histamine is mediated through H1-receptors and the relaxations of coronary and renal arteries induced by histamine are mediated through H2-receptors. It appears that H1- and H2-receptors interact with each other to produce potentiation of histamine-induced relaxations of mesenteric and gastro-epiploic arteries.