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Effects of (4S)-1-methyl-3-[(2S)-2-[N-((1S)-1-ethoxycarbonyl-3-phenylpropyl)amino]- propionyl]-2-oxoimidazolidine-4-carboxylic acid hydrochloride (TA-6366) on morphological change and mechanical property related to sodium ion permeability in the aorta of spontaneously hypertensive rats (SHRs) were examined, as compared with those of enalapril and captopril. Ten-week oral administration of TA-6366 (1 and 5 mg/kg/d) from 4 weeks of age impeded aortic media-thickening together with a rise in blood pressure in SHRs. Concomitantly, aorta weights in both groups were markedly decreased. The higher dose of TA-6366 almost fully suppressed the accelerated tension development induced by K(+)-free medium and decreased total sodium ion content in the aorta. These vascular effects of TA-6366 was more prominent than those of enalapril and captopril at 5 mg/kg/d. The difference in potencies on the above vascular parameters between TA-6366 and these drugs seemed to be mainly related to the difference in their antihypertensive activities. These results suggest that TA-6366 has preventive effects against progression of vascular diseases, particularly atherosclerosis, accompanied with hypertension.

journal of pharmacobio-dynamics

Effects of Long-Term Administration of (4S)-1-Methyl-3-{(2S)-2-(N-((1S)-1-ethoxycarbonyl-3-phenylpropyl)amino)propionyl}-2-oxoimidazolidine-4-carboxylic Acid Hydrochloride (TA-6366), a New Angiotensin I Converting Enzyme(ACE) Inhibitor, from the Pre-hypertensive Stage on Morphological Change and Mechanical Property Related to Sodium Ion Permeability in Aorta of Spontaneously Hypertensive Rats(SHRs).