Document Detail


A novel angiotensin II-receptor antagonist, 606A, induces regression of cardiac hypertrophy, augments endothelium-dependent relaxation and improves renal function in stroke-prone spontaneously hypertensive rats.
MedLine Citation:
PMID:  9541281     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
It is well-known that cardiac hypertrophy and arterial and renal dysfunction are serious complications of hypertension. Therefore, we investigated the chronic effects of 606A (2-propyl-3-[2'(1H-tetrazole-5-yl)biphenyl-4-yl]methyl-5-acetyl-4,5,6,7- tetrahydro imidazo [4,5-c]pyridine-4-carboxylic acid disodium salt), a novel AT1-receptor antagonist, on these complications of hypertension in stroke-prone spontaneously hypertensive rats (SHRSP) using Wistar Kyoto rats (WKY) as the control. After 8 weeks treatment from 16 weeks of age with 606A by a subcutaneously implanted osmotic pump, cardiac function, cardiac weight, acetylcholine-induced endothelium-dependent relaxation in the isolated aorta and renal function were estimated. Furthermore, wall thickness of the left ventricle was studied morphologically. We found that 606A (0.3 mg, 1 mg and 3 mg/head/day) dose-dependently lowered blood pressure without any effects on heart rate in SHRSP. Long-term treatments with 606A significantly reduced cardiac weight, left ventricular wall thickness and left ventricular end diastolic pressure, whereas it did not affect cardiac contractility. Endothelium-dependent relaxation of the aorta was recovered, and total protein excretion as well as total protein excretion/creatinine excretion ratio was reduced to the level of WKY by the treatment. These results suggest that 606A not only has a hypotensive effect but also protects cardiac, renal and vascular tissues from complications of hypertension. Thus, 606A could be an useful drug for treatment of hypertension.
Authors:
Y Hashimoto; Y Kurosawa; K Minami; K Fushimi; H Narita
Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  Japanese journal of pharmacology     Volume:  76     ISSN:  0021-5198     ISO Abbreviation:  Jpn. J. Pharmacol.     Publication Date:  1998 Feb 
Date Detail:
Created Date:  1998-05-13     Completed Date:  1998-05-13     Revised Date:  2004-11-17    
Medline Journal Info:
Nlm Unique ID:  2983305R     Medline TA:  Jpn J Pharmacol     Country:  JAPAN    
Other Details:
Languages:  eng     Pagination:  185-92     Citation Subset:  IM    
Affiliation:
Pharmaceutical Development Research Laboratory, Tanabe Seiyaku Co., Ltd., Toda, Saitama, Japan.
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MeSH Terms
Descriptor/Qualifier:
Acetylcholine / pharmacology
Animals
Antihypertensive Agents / blood,  pharmacology,  therapeutic use*
Cardiomegaly / drug therapy*,  physiopathology
Cerebrovascular Disorders / physiopathology
Endothelium, Vascular / drug effects*,  physiology
Kidney / physiopathology*
Male
Muscle Relaxation / drug effects
Organ Size
Rats
Rats, Inbred SHR
Receptors, Angiotensin / antagonists & inhibitors*
Tetrazoles / blood,  pharmacology,  therapeutic use*
Chemical
Reg. No./Substance:
0/606A compound; 0/Antihypertensive Agents; 0/Receptors, Angiotensin; 0/Tetrazoles; 51-84-3/Acetylcholine

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