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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.

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.
AuthorsY Hashimoto, Y Kurosawa, K Minami, K Fushimi, H Narita
JournalJapanese journal of pharmacology (Jpn J Pharmacol) Vol. 76 Issue 2 Pg. 185-92 (Feb 1998) ISSN: 0021-5198 [Print] Japan
PMID9541281 (Publication Type: Journal Article)
Chemical References
  • 606A compound
  • Angiotensin Receptor Antagonists
  • Antihypertensive Agents
  • Tetrazoles
  • Acetylcholine
Topics
  • Acetylcholine (pharmacology)
  • Angiotensin Receptor Antagonists
  • 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
  • Tetrazoles (blood, pharmacology, therapeutic use)

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