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

Japanese Journal of Pharmacology
Y HashimotoH Narita

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 t...Continue Reading

References

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Citations

Nov 7, 2002·Circulation Journal : Official Journal of the Japanese Circulation Society·Naoki IsobeHiroshi Kamiyama
Mar 24, 2009·Biomedicine & Pharmacotherapy = Biomédecine & Pharmacothérapie·Daiju FukudaMasataka Sata
Dec 13, 2005·Hypertension Research : Official Journal of the Japanese Society of Hypertension·Shinji TakaiMizuo Miyazaki
Feb 24, 2007·Journal of the Renin-angiotensin-aldosterone System : JRAAS·Vivencio BarriosRaúl Fernandez
Aug 8, 2009·Hypertension Research : Official Journal of the Japanese Society of Hypertension·Shinji TakaiMizuo Miyazaki
Apr 29, 1998·Journal of Cardiovascular Pharmacology·Y HashimotoS Murata

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