Document Detail


Effect of an angiotensin II receptor antagonist, CV-11974, and its prodrug, TCV-116, on production of aldosterone.
MedLine Citation:
PMID:  8013547     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
In dispersed rabbit adrenocortical glomerulosa cells, a non-peptide angiotensin II (AT1) receptor antagonist, CV-11974 (10(-10)-10(-5) M), competitively inhibited angiotensin II- or angiotensin III-stimulated aldosterone production, whereas PD123177, an angiotensin AT2 receptor antagonist, did not. CV-11974 inhibited aldosterone production induced by 4 mM K+ but not by 12 mM K+. CV-11974 had no effect on adrenocorticotropic hormone-stimulated aldosterone or corticosterone production, but inhibited angiotensin II-stimulated corticosterone production. In the rat, TCV-116, the prodrug of CV-11974, (0.1 and 1 mg/kg, p.o.) markedly reduced the elevation of both plasma aldosterone concentration and blood pressure induced by i.v. infusion of angiotensin II. In spontaneously hypertensive rats, TCV-116 at daily p.o. doses of 0.1, 1 and 10 mg/kg for 2 weeks caused a dose-dependent reduction of blood pressure and plasma aldosterone concentration without affecting plasma corticosterone. Thus, TCV-116 inhibited the induction of aldosterone production by not only exogenous but also endogenous angiotensin II.
Authors:
T Wada; Y Inada; T Sanada; M Ojima; Y Shibouta; M Noda; K Nishikawa
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Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  European journal of pharmacology     Volume:  253     ISSN:  0014-2999     ISO Abbreviation:  Eur. J. Pharmacol.     Publication Date:  1994 Feb 
Date Detail:
Created Date:  1994-07-26     Completed Date:  1994-07-26     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  1254354     Medline TA:  Eur J Pharmacol     Country:  NETHERLANDS    
Other Details:
Languages:  eng     Pagination:  27-34     Citation Subset:  IM    
Affiliation:
Pharmaceutical Research Laboratories I, Takeda Chemical Industries, Ltd., Osaka, Japan.
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MeSH Terms
Descriptor/Qualifier:
Administration, Oral
Adrenocorticotropic Hormone / pharmacology
Aldosterone / biosynthesis*,  blood
Angiotensin II / administration & dosage,  pharmacology
Angiotensin III / administration & dosage,  pharmacology
Animals
Benzimidazoles / administration & dosage,  pharmacology*
Biphenyl Compounds / administration & dosage,  pharmacology*
Cells, Cultured
Corticosterone / biosynthesis
Hypertension / metabolism,  physiopathology
Imidazoles / administration & dosage,  pharmacology
Infusions, Intravenous
Male
Pyridines / administration & dosage,  pharmacology
Rabbits
Rats
Rats, Inbred SHR
Rats, Wistar
Receptors, Angiotensin / antagonists & inhibitors*
Tetrazoles / administration & dosage,  pharmacology*
Zona Glomerulosa / cytology,  drug effects*,  metabolism
Chemical
Reg. No./Substance:
0/Benzimidazoles; 0/Biphenyl Compounds; 0/Imidazoles; 0/Pyridines; 0/Receptors, Angiotensin; 0/Tetrazoles; 11128-99-7/Angiotensin II; 114785-12-5/PD 123177; 12687-51-3/Angiotensin III; 139481-59-7/candesartan; 145040-37-5/candesartan cilexetil; 50-22-6/Corticosterone; 52-39-1/Aldosterone; 9002-60-2/Adrenocorticotropic Hormone

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