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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概要

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• 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.

• 社団法人 日本薬理学会の論文

著者

• Fushimi Keiko

  Lesd Optimization Research Laboratory Tanabe Seiyaku Co. Ltd.

• NARITA Hiroshi

  Pharmaceutical Development Research Laboratory, Tanabe Seiyaku Co., Ltd.

• Narita Hirokazu

  Research Laboratories Toyama Chemical Co. Ltd

• Narita H

  Research Laboratories Toyama Chemical Co. Ltd

• HASHIMOTO Yoshihiro

  Pharmaceutical Development Research Laboratory, Tanabe Seiyaku Co., Ltd.

• KUROSAWA Yukie

  Pharmaceutical Development Research Laboratory, Tanabe Seiyaku Co., Ltd.

• MINAMI Koichi

  Pharmaceutical Development Research Laboratory, Tanabe Seiyaku Co., Ltd.

• HASHIMOTO Yoshihiro

  Discovery Research Laboratory, Tanabe Seiyaku Co., Ltd.

• Kurosawa Yukie

  Pharmaceutical Development Research Laboratory Tanabe Seiyaku Co. Ltd.

• Minami Kouichiro

  Department Of Anesthesiology And Critical Care Medicine Jichi Medical University

• Hashimoto Yoshihiro

  Discovery Research Laboratory Tanabe Seiyaku Co. Ltd.

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