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).
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.
Kubo
M
M
Pharmacological Research Laboratory, Tanabe Seiyaku Co., Ltd., Osaka, Japan.
Kobayashi
K
K
Ishida
R
R
D000806:Angiotensin-Converting Enzyme Inhibitors / Q000008:administration & dosage / Q000494:pharmacology*; D000818:Animals; D001011:Aorta / Q000187:drug effects* / Q000378:metabolism; D001794:Blood Pressure / Q000187:drug effects; D001835:Body Weight / Q000187:drug effects; D002216:Captopril / Q000494:pharmacology; D006332:Cardiomegaly / Q000517:prevention & control; D004305:Dose-Response Relationship, Drug; D004656:Enalapril / Q000494:pharmacology; D007093:Imidazoles / Q000008:administration & dosage / Q000494:pharmacology*; D048289:Imidazolidines; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects; D009929:Organ Size / Q000187:drug effects; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D012964:Sodium / Q000378:metabolism*
D000806:Angiotensin-Converting Enzyme Inhibitors; D007093:Imidazoles; D048289:Imidazolidines; D004656:Enalapril; D002216:Captopril; D012964:Sodium; C065166:imidapril