Antihypertensive Action of a New Angiotensin Converting Enzyme Inhibitor, (R)-3-[(S)-1-Carboxy-5-(4-Piperidyl)pentyl]amino-4-Oxo-2,3,4,5-Tetrahydro-1,5-Benzothiazepine-5-Acetic Acid (CV-5975), in Various Hypertensive Models

The antihypertensive activity of a new angiotensin converting enzyme (ACE) inhibitor, CV-5975, (R)-3-[(S)-1 -carboxy-5-(4-piperidyl)pentyl]amino-4-oxo-2,3,4,5-tetrahydro-1,5-benzodiazepine-5-acetic acid, was examined in normotensive rats and various hypertensive animal models. In spontaneously hyper...

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Bibliographic Details
Published in:Japanese Journal of Pharmacology 1988, Vol.47 (3), p.311-322
Main Authors: INADA, Yoshiyuki, TANABE, Masao, KAWAZOE, Katsuyoshi, NISHIKAWA, Kohei
Format: Article
Language:eng ; jpn
Subjects:
Antihypertensive agents
Biological and medical sciences
Cardiovascular system
Medical sciences
Pharmacology. Drug treatments
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Summary:The antihypertensive activity of a new angiotensin converting enzyme (ACE) inhibitor, CV-5975, (R)-3-[(S)-1 -carboxy-5-(4-piperidyl)pentyl]amino-4-oxo-2,3,4,5-tetrahydro-1,5-benzodiazepine-5-acetic acid, was examined in normotensive rats and various hypertensive animal models. In spontaneously hypertensive rats, CV-5975 (1 to 10 mg/kg, p.o.) had a dose-related, sustained antihypertensive action, which was more potent and longer than that of enalapriL The potency and duration of action of CV-5975 was intensified when it was administered repeatedly or combined with hydrochlorothiazide. CV-5975 (1 mg/kg, p.o.) inhibited the ACE activity of plasma and tissues; inhibition on the ACE activity of the aorta, kidney, and brain was marked when CV-5975 was administered repeatedly. In 2-kidney, 1 clip hypertensive rats (1 to 10 mg/kg, p.o.) and dogs (0.3 and 1 mg/kg, p.o.), CV-5975 had a marked, sustained antihypertensive action, which was more marked than that of enalapril. In normotensive rats (10 mg/kg), 1 -kidney, 1 clip hypertensive rats (3 and 10 mg/kg), and hyporeninemic DOCA/salt hypertensive rats (1 to 10 mg/kg/day), CV-5975 administered orally once or repeatedly reduced blood pressure, whereas enalapril did not. These results indicate that CV-5975 is a potent and long-lasting antihypertensive agent, the action of which is mediated primarily by inhibiting ACE activity and partly by some unknown mechanisms.
ISSN:0021-5198
1347-3506
DOI:10.1016/S0021-5198(19)43215-0