Pharmacology of a Phosphorus-Containing Novel Angiotensin Converting Enzyme Inhibitor, SQ 29 852 in Anesthetized Dogs
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概要
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The effects of (S)-1 [6-amino-2 [[hydrozy (4-phenylbutyl) phosphinyl] oxy]-1-oxohexyl]-L-proline (SQ 29 852), a phosphorus-containing novel angiotensin converting enzyme inhibitor (ACEI), which is synthesized aiming an ACEI with long-lasting activity and with few side effects, were studied using anesthetized dogs. SQ 29 852 was equipotent with captopril to modify blood pressure response of the animals to angiotensin I (Ang I) and bradykinin (Bdk). An intravenous infusion of SQ 29 852 at 0.1 mg/kg/min for 30 min caused a remarkable hypotension without reflex tachycardia in open-chest dogs. In these animals cardiac contractility (dP/dt_<max> of left ventricular pressure) appeared to be reduced by SQ 29 852 without any changes in right atrial pressure (RAP), left ventricular end-diastolic pressure (LVEDP) and aortic blood flow (AoF, cardiac output). In sodium-restricted dogs, the hypotension and renal vasodilation by SQ 29 852 (at 0.01,0.1,and 1 mg/kg, i.v.) were slightly pronounced compared with animals fed with normal diet. It is demonstrated from these results that SQ 29 852 has comparable potency with captopril to inhibit angiotensin converting enzyme (ACE) activity and as common a pharmacological profile as ACEI. SQ 29 852 may be a favorable anti-hypertensive agent, if its long-lasting activity and few side effects are confirmed.
- 公益社団法人日本薬学会の論文
著者
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Konishi Chika
Department of Cardiology, Kyoto Prefectural Rakuto Hospital
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Ono Hiroshi
Department of Internal Medicine, the Division of Respiratory Medicine, Infection Diseases, and Oncol
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Konishi Chika
食品薬品安全センター秦野研究所
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Konishi Chika
Department Of Pharmacology And Toxicology Hatano Research Institute Food And Drug Safety Center
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Konishi Chika
Department Of Cardiology Kyoto Prefectural Rakuto Hospital
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Ohara N
Department Of Pharmacology And Toxicology Hatano Research Institute
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OHARA Naoki
Department of Pharmacology and Toxicology, Hatano Research Institute, Food and Drug Safety Center
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YOKOTA Syunji
Department of Pharmacology and Toxicology, Hatano Research Institute, Food and Drug Safety Center
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SHUKUNOBE Kazuichi
Department of Pharmacology and Toxicology, Hatano Research Institute, Food and Drug Safety Center
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Ono H
Univ. Tokyo Tokyo Jpn
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Ogawa N
Department Of Pharmacology Ehime University School Of Medicine
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Yokota Syunji
First Laboratory Of Toxicology Hatano Research Institute Food And Drug Satety Center
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Yokota Syunji
Department Of Pharmacology And Toxicology Hatano Research Institute
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Ohara Naoki
Department Of Pharmacology And Toxicology Hatano Research Institute
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Ogawa N
Department Of Fundamental Science Gifu National College Of Technology
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Ono Hiroshi
Department Of Agronomy Faculty Of Agriculture Tottori University
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Shukunobe Kazuichi
Department Of Pharmacology And Toxicology Hatano Research Institute Food And Drug Safety Center
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