Involvement of cyclic AMP in the positive inotropic effect of OPC-8212, a new cardiotonic agent, on the canine ventricular muscle.
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概要
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OPC-8212 is a new positive inotropic drug which scarcely produces an increase in heart rate and vasodilatation. The positive inotropic effect of OPC-8212 was investigated in relation to cyclic AMP metabolism in canine isolated ventricular muscle. The positive inotropic effect of OPC-8212 was accompanied by accumulation of cyclic AMP in the tissue: the cyclic AMP level was elevated before the increase in force of contraction and elevated in a concentration-dependent manner in the presence of a β-adrenoceptor antagonist, atenolol (10<SUP>-6</SUP> M). The OPC-8212-induced increases in force of contraction and cyclic AMP level were abolished by carbachol (3×10<SUP>-6</SUP> M). The relationship between the force of contraction and cyclic AMP level in the presence of OPC-8212 was changed by neither carbachol nor isoproterenol. OPC-8212 enhanced the positive inotropic effect of isoproterenol as cyclic AMP phosphodiesterase inhibitors did. OPC-8212 shortened the time to peak tension and had a tendency to shorten the relaxation time of single contractions. These results altogether suggest that change in cyclic AMP metabolism is involved at least in the positive inotropic effect of OPC-8212 on canine ventricular muscle.
- 公益社団法人 日本薬理学会の論文
著者
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Yanagisawa Teruyuki
Department Of Molecular Pharmacology Tohoku University Graduate School Of Medicine
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Endoh Masao
Department Of Cardiovascular Pharmacology Yamagata University School Of Medicine
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TAIRA Norio
Department o f Pharmacology, Tohoku University, School of Medicine
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