Bradycardic effects of AQ-A 39(falipamil) in situ and in isolated, blood-perfused dog hearts comparison with alinidine and verapamil.:Comparison with Alinidine and Verapamil
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概要
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The cardiovascular effects of a specific bradycardic agent, AQ-A 39, were investigated in intact donor dogs and isolated and cross-perfused dog heart preparations. Intravenous administration of AQ-A 39 (10-1000μg/kg) to the donor dog caused a dose-dependent heart rate de-crease in the donor dog and a decreased atrial rate in the isolated atrium perfused by the donor's blood. The arterial blood pressure of the donor dog and contractile force of the atrial preparation were unchanged or slightly decreased. The direct injection of AQ-A 39 (1-300μg) into the sinus node artery of the isolated atrium caused dose-dependent negative chronotropic and slight, transient positive inotropic responses. Alinidine and verapamil caused marked negative chronotropic and inotropic re-sponses. The negative chronotropic effect of AQ-A 39 was not modified by atropine. However, it was enhanced slightly but significantly by pro-pranolol, indicating that AQ-A 39-induced bradycardia was antagonized partly by beta-adrenoceptor function. These results confirmed that AQ-A 39 selectively reduced sinus rate by a direct action on the sinus node. Furthermore, the potency of the bradycardic action, compared with the decrease in contractility, was greater than for alinidine or verapamil. AQ-A 39 (300μg) tended to depress norepinephrine (NE)-induced positive chronotropic but not inotropic effects in isolated atria. By contrast, verapamil (3-10μg) significantly depressed the NE-induced positive iso-tropic but not the chronotropic effect, and propranolol (10μg) sup-pressed both cardiac effects of NE. These data suggest that the AQ-A 39-induced, selective attenuation of the NE-induced chronotropic effect is not due to either calcium channel blockade or beta-adrenoceptor an-tagonism.
- International Heart Journal刊行会の論文
著者
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Furukawa Yasuyuki
Department Of Pharmacology Shinshu University School Of Medicine
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Haniuda Masayuki
Department Of Chest Surgery Aichi Medical University
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Chiba Shigetoshi
Departmen T Of Pharmacology Shinshu University School Of Medicine
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Akahane Kunio
Department of Pharmacology, Shinshu University School of Medicine
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OGIWARA Yasuhiro
Department of Pharmacology, Shinshu University School of Medicine
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