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.