Influence of species and drug pretreatment on the metabolic oxidation of cimetidine and metiamide.
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When histamine was injected into the sinus node artery of isolated dog atrium perfused with arterial blood led from a carotid artery of the heparinized support dog, positive chronotropic and inotropic effects were dose-relatedly induced at a dose range of 0.1 to 100 microgram. The threshold dose for ind1cing these positive effects was approximately 0.3 microgram. These positive responses to histamine were not blocked by tetrodotoxin, desmethylimipramine and alprenolol. These positive effects of histamine were also not significantly influenced by treatment with a histamine H2 receptor antagonist, tripelennamine or diphenhydramine, which enhanced the actions of norepinephrine. From these results, it is suggested that in the dog atrium, histamine causes positive chronotropic and inotropic effects via histamine H1 receptors.
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