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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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′(1<I>H</I>-tetrazole-5-yl)biphenyl-4-yl]methyl-5-acetyl-4, 5, 6, 7-tetrahydro imidazo[4, 5-<I>c</I>]pyridine-4-carboxylic acid disodium salt), a novel AT<SUB>1</SUB>-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.


  • The Japanese Journal of Pharmacology

    The Japanese Journal of Pharmacology 76(2), 185-192, 1998-02

    The Japanese Pharmacological Society

References:  30

Cited by:  2


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