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.
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- Hashimoto Yoshihiro
- Pharmaceutical Development Research Laboratory, Tanabe Seiyaku Co., Ltd.
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- Kurosawa Yukie
- Pharmaceutical Development Research Laboratory, Tanabe Seiyaku Co., Ltd.
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- Minami Koichi
- Pharmaceutical Development Research Laboratory, Tanabe Seiyaku Co., Ltd.
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- Fushimi Keiko
- Lead Optimization Research Laboratory, Tanabe Seiyaku Co., Ltd.
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- Narita Hiroshi
- Pharmaceutical Development Research Laboratory, Tanabe Seiyaku Co., Ltd.
Bibliographic Information
- Other Title
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- A Novel Angiotensin 2-Receptor Antagonist,606A,Induces Regression of Cardiac Hypertrophy,Augments Endothelium-Dependent Relaxation and Improves Renal Function in Stroke-Prone Spontaneously Hypertensive Rats
- Novel Angiotensin 2-Receptor Antagonist
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Abstract
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.
Journal
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- The Japanese Journal of Pharmacology
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The Japanese Journal of Pharmacology 76 (2), 185-192, 1998
The Japanese Pharmacological Society
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Details
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- CRID
- 1390001204286040320
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- NII Article ID
- 10008191538
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- NII Book ID
- AA00691188
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- COI
- 1:CAS:528:DyaK1cXht12ntrk%3D
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- ISSN
- 13473506
- 00215198
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- NDL BIB ID
- 4416244
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- PubMed
- 9541281
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- Web Site
- https://ndlsearch.ndl.go.jp/books/R000000004-I4416244
- https://api.elsevier.com/content/article/PII:S0021519819312272?httpAccept=text/xml
- https://api.elsevier.com/content/article/PII:S0021519819312272?httpAccept=text/plain
- https://www.jstage.jst.go.jp/article/jjp/76/2/76_2_185/_pdf
- https://search.jamas.or.jp/link/ui/1998207225
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- Text Lang
- en
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- Data Source
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- JaLC
- NDL
- Crossref
- PubMed
- CiNii Articles
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- Abstract License Flag
- Disallowed