Antihypertensive Action of a Non-Sulfhydryl Angiotensin Converting Enzyme Inhibitor (CV-3317) in Various Hypertensive Models

The antihypertensive action of N-[N-[(S)-1-ethoxycarbonyl-3-phenylpropyl]-L-alanyl]-N-(indan-2-yl)glycine hydrochloride (CV-3317), a nonsulfhydryl compound characterized as an angiotensin converting enzyme inhibitor in our previous work, was examined in hypertensive animal models. In 2-kidney, 1 cli...

Full description

Saved in:
Bibliographic Details
Published in:Japanese Journal of Pharmacology 1986, Vol.42(1), pp.1-8
Main Authors: INADA, Yoshiyuki, TANABE, Masao, SHIBOUTA, Yumiko, KAWAZOE, Katsuyoshi, NISHIKAWA, Kohei, KIKUCHI, Shintaro
Format: Article
Language:English
Subjects:
Angiotensin-Converting Enzyme Inhibitors
Animals
Antihypertensive Agents
Biological and medical sciences
Cardiovascular system
Decerebrate State
Desoxycorticosterone
Hypertension - chemically induced
Hypertension - physiopathology
Hypertension, Renal - drug therapy
Indans - pharmacology
Indenes - pharmacology
Male
Medical sciences
Pharmacology. Drug treatments
Rats
Rats, Inbred SHR
Rats, Inbred Strains
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:The antihypertensive action of N-[N-[(S)-1-ethoxycarbonyl-3-phenylpropyl]-L-alanyl]-N-(indan-2-yl)glycine hydrochloride (CV-3317), a nonsulfhydryl compound characterized as an angiotensin converting enzyme inhibitor in our previous work, was examined in hypertensive animal models. In 2-kidney, 1 clip hypertensive rats and dogs, CV-3317 (3 and/or 10 mg/kg, p.o.) produced a sustained antihypertensive action of about 15 to 25 mmHg. Daily oral administrations of CV-3317 (1 to 10 mg/kg/day) to spontaneously hypertensive rats (SHR) for 5 weeks produced a sustained antihypertensive action of 20 to 40 mmHg. When CV-3317 (3 mg/kg) was combined with hydrochlorothiazide (10 mg/kg), its antihypertensive action was intensified in potency and duration. CV-3317 (30 mg/kg) induced a slight hypotension (5 to 10 mmHg) in normotensive rats, but had no effect on the blood pressure of 1-kidney, 1 clip hypertensive rats and on that of a low renin type of DOCA/salt hypertensive rat. The .antihypertensive activity of CV-3317 was more potent than that of captopril. In pithed SHR, the pressor response* induced by an electrical stimulation of the preganglionic sympathetic nerve, but not the pressor response to norepinephrine, was attenuated by both agents (0.3 mg/kg, i.v.). Both agents may exert their antihypertensive action not only primarily by inhibiting the renin-angiotensin system, but also by inhibiting norepinephrine release from the sympathetic nerve terminals indirectly by reducing the formation of vascular angiotensin II.
ISSN:0021-5198
1347-3506
DOI:10.1254/jjp.42.1