Absence of Blocking Effect of Burimamide and Metiamide on Positive Chronotropic and Inotropic Responses to Histamine in Isolated Dog Atrium

Abstract

Abstract-Whenhistamine 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 Pg. The threshold dose for inducing these positive effects was approximately 0.3 ; eg. 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 an tagonist, burimamide or metiamide.However, these histamine-induced positive chronotropic and inotropic effects were significantly suppressed by an adequate dose of histamine 1-11 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 his tamine H1 receptors. (1-4). However, in isolated dog heart, there is no available report for existence of histamine H2 receptors.Thus, in the present experiments, an attempt was made to investigate the characteristics of cardiac histamine receptors in isolated dog atrium by means of the selective histamine H2 receptor blocking agents, burimamide or metiamide, using the isolated, blood-perfused atrium preparation of the dog (5, 6). Moreover, the action of histamine was analysed by use of pharmacological key drugs, i.e., histamine H1 receptor antagonists (tripelennamine and diphenhydramine), alprenolol which is a potent adrenergic beta-receptor blocking agent, desmethylimipramine which blocks uptake mechanism in the sympathetic nerve terminals, and tetrodotoxin which blocks nerve excitation. MATERIALS AND METHODSTwenty-five mongrel dogs, weighing 11-16 kg, were anesthetized with sodium pen

On the Histamine Receptor of the Canine Myocardium and Coronary Vasculature

“…In contrast, the positive chronotropic effect was abolished with Hl-receptor antagonist, and such is in agreement with the recent findings of Chiba (10). Thus, unlike the histamine-receptor in the guinea pig atrium, the histamine receptor in the dog atrial myocardium subserving the positive chronotropic effect is to be classified as H1-type receptor.…”

Mechanism of positive chronotropic and inotropic effects induced by 4-methylhistamine.

“…Thus, in the dog heart, the histamine-induced positive effects appeaved to be mediated via histamine Hl-receptors (1). However, larger doses of histamine frequently induced sudden sinus arrest, as shown in the present study and in the previous paper (1). Thus, the sinus arrest may be also produced through histamine Hl receptors.…”

“…Previously Chiba (1) reported that histamine produced positive chronotropic and inotropic responses of the dog atrial muscle. Since these positive responses to histamine were blocked by a histamine Hl-receptor antagonist , tripelennamine or diphenhydramine, but were not influenced by a H2-receptor antagonist, burimamide or metiamide, or alprenolol, an adrenergic beta-blocking agent, these responses might be due to stimulation of H1 receptors.…”

“…Previously, one of us reported that histamine-induced positive chronotropic and iso tropic effects were not blocked by the adrenergic beta-blockade but were inhibited by hista mine Hl-receptor blockade (1). Thus, in the dog heart, the histamine-induced positive effects appeaved to be mediated via histamine Hl-receptors (1).…”

Histamine H2-receptor mediated positive dromotropic effect in the canine atrioventricular node.

“…However, histamine itself attenuated the tachycardia produced by stimulation of cardiac sympathet ic nerves via presynaptic mechanisms (8,14,15). Furthermore, positive chronotropic and positive inotropic effects of histamine in the isolated dog atrium were not blocked by tetrodotoxin (a blocker of nerve excitation), desmethylimipramine (an uptake blocker) and alprenolol (a beta-blocker), although desmethyl-imipramine slightly but insignifi cantly suppressed the histamine-induced positive chronotropic effect (16). Even in the present experiments, both the shortenings were never abolished by atenolol which almost completely abolished the noradrena line-induced shortening (Fig.…”