Comparison of acute hemodynamic effects of MC-838, a new angiotensin-converting enzyme inhibitor, with captopril in anesthetized dogs.
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概要
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Effects of a new angiotensin-converting enzyme inhibitor, N-[3-(N-cyclohexanecarbonyl-D-alanylthio)-2-methylpropanoyl]-L-proline calcium (MC-838), on the systemic and coronary circulation were evaluated in anesthetized dogs, and the effects were compared with those of captopril. Administration of MC-838 (0.1, 0.3, 1.0 and 3.0 mg/kg, i.v.) produced a gradual and dose-dependent decline in aortic pressure associated with no marked changes in coronary blood flow, heart rate and LVdP/dt. Captopril (0.01, 0.03, 0.1 and 0.3 mg/kg, i.v.) also caused a dose-related decrease in aortic pressure, but the significant hypotension appeared more rapidly than that of MC-838. Both MC-838 and captopril inhibited selectively the pressor response to angiotensin I in a dose-related manner. The doses of MC-838 and captopril to lower mean aortic pressure by 10 mmHg from the pre-drug value were 2.8 mg/kg and 0.03 mg/kg, respectively; those of these drugs to cause 50% inhibition of angiotensin I-pressor response were 1.0 mg/kg and 0.04 mg/kg, respectively. When administration of MC-838 (3.0 mg/kg) was repeated three times at a 30 min-interval, the second and third injections caused no additional hypotension, while each of the repeated injections of captopril (0.3 mg/kg) produced significant hypotension. These results indicate that MC-838 inhibits angiotensin I-conversion and decreases systemic blood pressure more slowly and persistently than captopril in anesthetized dogs.
- 公益社団法人 日本薬理学会の論文
著者
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Noguchi Katsuhiko
Department Of Pharmacalogy School Of Medicine Faculty Of Medicine University Of The Ryukyus
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Sakanashi Matao
Department Of Pharmacology And Department Of Pediatrics School Of Medicine University Of The Ryukyus
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SUNAGAWA Ryuji
Department of Pharmacology
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Miyamoto Yoshimasa
Department Of Pharmacalogy School Of Medicine Faculty Of Medicine University Of The Ryukyus
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Kato Takayuki
Department Of Applied Chemistry Faculty Of Science And Engineering Saga University
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SUNAGAWA Ryuji
Department of Pharmacology, School of Medicine, Faculty of Medicine, University of the Ryukyus
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