Lipophilic properties of various inhibitors of the angiotensin I - converting enzyme (ACE) and their diffusion through cultured endothelium

The aim of our study was to determine the lipophilic properties of various inhibitors of the angiotensin I converting enzyme (ACE). The background for these investigations was the discovery that a formation of angiotensin II by renin angiotensin system is significantly involved in the actions of this hormone system. Consequently, the question arose whether these tissue specific and in part intracellular systems may be influenced differentially by ACE inhibitors with different physicochemical properties. Lipophilia of ACE inhibitors was characterized by the extraction coefficient (E) in a octanol-water system. All diacids forms of ACE inhibitors are dissociated at a pH of 7.4 and nearby extractable into octanol (E < 10%). In contrast, the extraction coefficients of the parent substances showed marked differences with 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 layer of cultered bovine aortic endothelium cells was investigated. The diffusion rates of captopril, enalapril, enalaprilat, ramipril and ramiprilat were similar indicating that endothelium constitutes no specific barrier for the passage of ACE inhibitors into the vessel wall.