A Na^+/Ca^<2+> Exchanger Inhibitor, KB-R7943, Caused Negative Inotropic Responses and Negative Followed by Positive Chronotropic Responses in Isolated, Blood-Perfused Dog Heart Preparations
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概要
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Effects of a Na+/Ca2+ exchanger inhibitor, KB-R7943(2-[2-[4-(4-nitrobenzyloxy)phenyl]ethyl]isothiourea methanesulfonate), on the sinoatrial nodal pacemaker activity, atrial contractility and ventricular contractility were investigated in the isolated and blood-perfused right atrium and left ventricle of the dog.KB-R7943(0.03-3μmol)induced negative inotropic effects and negative followed by positive chronotropic effects in the right atrium and negative inotropic effects in the left ventricle.Neither atropine nor hexamethonium affected the cardiac responses to KB-R7943.Propranolol attenuated the positive chronotropic response to KB-R7943 but imipramine did not.Tetrodotoxin potentiated the positive chronotropic response to KB-R7943 in 6 of 11 isolated atria.When NaCl infusion increased atrial contractile force and atrial rate, KB-R7943-induced negative inotropic and chronotropic responses were attenuated in a dose-dependent manner.CaCl2 infusion potentiated the negative chronotropic response to KB-R7943 but did not affect the inotropic response significantly.On the other hand, ouabain(17nmol)attenuated the negative inotropic response, but not chronotropic response, to KB-R7943.These results suggest that KB-R7943-induced cardiac effects relate to the Na+ activity, probably mediated through the Na+/Ca2+ exchanger, and the Na+/Ca2+ exchanger modifies the pacemaker activity and myocardial contractility in the dog heart.
- 社団法人 日本薬理学会の論文
- 2000-02-01
著者
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TSUBOI Masato
Department of Astronomy, School of Science, The University of Tokyo
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TSUBOI Masato
Institute of Astrophysics and Planetary Science, Ibaraki University
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Chiba Shigetoshi
Department Of Molecular Pharmacology Shinshu University School Of Medicine
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Hirose Masamichi
Department of Molecular Pharmacology, Shinshu University School of Medicine
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NAKAJIMA Koichi
Department of Immunology, Osaka City University Graduate School of Medicine
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Tsuboi M
Institute Of Astrophysics And Planetary Science Ibaraki University
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ZHAO Ding
Department of Natural Product Chemistry, School of Pharmaceutical Sciences, Hebei Medicinal Universi
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Zhao Ding
Department Of Natural Product Chemistry School Of Pharmaceutical Sciences Hebei Medicinal University
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Zhao Ding
Department Of Pharmacology Shinshu University School Of Medicine
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Kurogouchi Fumio
Department Of Pharmacology Shinshu University School Of Medicine
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FURUKAWA Yasuyuki
Department of Pharmacology, Shinshu University School of Medicine
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Furukawa Yasuyuki
Department Of Pharmacology Shinshu University School Of Medicine
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Chiba S
信州大学 薬理
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Hirose Masamichi
Department Of Pharmacology Shinshu University School Of Medicine
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Hirose Masamichi
Department Of Molecular Pharmacology Shinshu University School Of Medicine
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Nakajima Koichi
Department Of Pharmacology Shinshu University School Of Medicine
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Nakajima Koichi
Department Of Immunology Osaka City University Graduate School Of Medicine
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Hirose Masamichi
Department Of Molecular And Cellular Pharmacology Iwate Medical University School Of Pharmaceutical
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Chiba Shigetoshi
Departmen T Of Pharmacology Shinshu University School Of Medicine
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Tsuboi Masato
Department Of Astronomy School Of Science The University Of Tokyo
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