Cardiovascular effects and plasma levels of denopamine (TA-064), a new positive inotropic agent, in chronically instrumented dogs.
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概要
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Cardiovascular effects of denopamine (TA-064), a new positive inotropic agent, in chronically instrumented dogs were investigated following intravenous and oral administration. In the conscious state, denopamine (0.5-4 μg/kg/min, i.v. infusion) increased LV dp/dt<SUB>max</SUB>, cardiac output, stroke volume in a dose-dependent manner, and it decreased left ventricular end-diastolic pressure, total peripheral resistance and PQ interval. Denopamine produced an increase in LV dp/dt<SUB>max</SUB> by 90% at a rate of 4 μg/kg/min with slightly increasing systemic blood pressure and heart rate. In the same dogs after anesthetizing with pentobarbital, denopamine in the same dose range showed more marked positive inotropic effects and less changes in cardiac output and total peripheral resistance than in conscious dogs. Other cardiovascular effects of denopamine were qualitatively similar to conscious dogs. These effects of denopamine were diminished by treatment with propranolol. Oral administration of denopamine to conscious dogs (0.1-0.4 mg/kg) produced a rise in LV dp/dt<SUB>max</SUB> dose-dependently, and denopamine at a dose of 0.4 mg/kg increased LV dp/dt<SUB>max</SUB> by 66%, this effect lasting for 7 hr. Heart rate and blood pressure were not affected significantly. Effects on other cardiovascular parameters were changed in the same direction as intravenous administration. The increase in LV dp/dt<SUB>max</SUB> corresponded well with the changes in plasma levels of denopamine in conscious dogs by both intravenous and oral administration. Denopamine showed a selective positive inotropic effect in chronically instrumented dogs, and its positive inotropic action was more marked in the myocardium depressed with an anesthetizing dose of pentobarbital than in the conscious state.
- 公益社団法人 日本薬理学会の論文
著者
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NAGAO TAKU
Biological Research Laboratory, Tanabe Seiyaku Co., Ltd.
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Yabana Hideo
Biological Research Laboratory Tanabe Seiyaku Co. Ltd.
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IKEO Tomihiro
Biological Research Laboratory, Tanabe Seiyaku Co., Ltd.
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NAKAJIMA Hiromichi
Biological and Chemical Reseach Labolatories, Tanabe Seiyaka Co., Ltd.
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NAGAO Taku
Biological Research Laboratories, Tauabe Seiyaku Co., Ltd.
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SUZUKI Toshikazu
Biological Research Laboratory, Tanabe Seiyaku Co., Ltd.
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