The Lipophilic Properties of Angiotensin I-Converting Enzyme Inhibitors Do Not Influence Their Diffusion Through Cultured Endothelium

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概要

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• The background for these investigations was the discovery that formation of angiotensin II by the renin angiotensin system can take place in extravascular tissues (e.g., cardiomyocytes and neurons) and within single cells. Consequently, the question arose about whether such tissue-based systems might be differentially influenced by angiotensin I-converting enzyme (ACE) inhibitors with distinct physicochemical properties. Therefore, the aim of this study was to investigate how the membrane penetration of various ACE inhibitors depends on their lipophilia. All diacid forms of ACE inhibitors are dissociated at a pH of 7.4 and scarcely extractable into octanol (extraction coefficient <10%). In contrast, the extraction coefficients of the parent substances showed marked differences in the following order of increasing lipophilia: enalapril=perindopril<captopril=ceranapril<ramipril<quinapril<HOE288=zofenopril<fosinopril<HOE065. For selected substances, the kinetics of diffusion through a monolayer of cultured bovine aortic endothelium were determined. The diffusion rates (expressed as half lives) of captopril (59.6 min), enalapril (53.4 min), enalaprilat (50.8 min), ramipril (56.9 min) and ramiprilat (51.1 min) are similar indicating: 1) that penetration is independent on lipophilia and 2) that endothelium constitutes no specific barrier for the passage of ACE inhibitors into the vessel wall.

• 社団法人 日本薬理学会の論文
• 1999-12-01

著者

• Raasch W

  Institute Of Experimental And Clinical Pharmacology And Toxicology Medical University Of Lubeck

• Dendorfer Andreas

  Institute Of Experimental And Clinical Pharmacology And Toxicology Medical University Of Lubeck

• Raasch Walter

  Institute Of Experimental And Clinical Pharmacology And Toxicology Medical University Of Lubeck

• Dominiak P

  Institute Of Experimental And Clinical Pharmacology And Toxicology Medical University Of Lubeck

• Dominiak Peter

  Institute For Experimental And Clinical Pharmacology And Toxicology Medical University Of Lubeck

• BALL Benedikt

  Institute of Experimental and Clinical Pharmacology and Toxicology, Medical University of Lubeck

• Ball Benedikt

  Institute Of Experimental And Clinical Pharmacology And Toxicology Medical University Of Lubeck

• Dendorfer Andreas

  Institute of Experimental and Clinical Pharmacology and Toxicology, Medical University of Lubeck

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