Effects of Glibenclamide on Negative Cardiac Responses to Cholinerg and Purinergic Stimuli and Cromakalim in the Isolated Dog Heart.
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概要
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We investigated the effects of an ATP-sensitive K<SUP>+</SUP> channel blocker, glibenclamide, on the negative chronotropic and inotropic responses to intracardiac parasympathetic nerve stimulation, acetylcholine (ACh, a muscarinic receptor agonist), ATP (a P<SUB>2</SUB>-purinergic receptor agonist), adenosine (a P<SUB>1</SUB>-purinergic receptor agonist) and cromakalim (a potassium channel opener) in the isolated, blood-perfused canine right atrium or left ventricle. A high dose of glibenclamide (3 μmol) did not affect the negative chronotropic and inotropic responses to parasympathetic stimulation (frequencies of 1-30 Hz), although it slightly but significantly attenuated the negative cardiac responses to exogenous ACh (0.3-10 nmol). Furthermore, adenosine (0.03-0.3 μmol)-induced negative chronotropic and inotropic responses were significantly inhibited by glibenclamide (3 μmol), but ATP (0.01-1 μmol)-induced negative cardiac responses were not affected. A cumulative administration of cromakalim (0.01-1 μmol) dose-dependently caused much greater decreases in the contractile force of atrial and ventricular muscles than in sinus rate. Glibenclamide (0.3-3 μmol) similarly blocked the negative chronotropic and inotropic responses to cromakalim in a dose-depend ent manner. These results suggest that glibenclamide modifies the negative cardiac responses to parasympathetic activation both in pre and postjunctional sites and the responses to adenosine but not to ATP at K<SUP>+</SUP> channels in the dog heart, although the modifications are minor under physiological conditions.
- 公益社団法人 日本薬理学会の論文
著者
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Furukawa Yasuyuki
Department Of Pharmacology Shinshu University School Of Medicine
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Murakami Makoto
Department Of Agricultural Engineering Faculty Of Agriculture Hokkaido University
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Chiba Shigetoshi
Departmen T Of Pharmacology Shinshu University School Of Medicine
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Chiba Shigetoshi
Department of Pharmacology, Shinshu University School of Medicine
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