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

It is well-known that cardiac hypertrophy and arterial and renal dysfu nction are serious complications of hypertension. Therefore, we invest igated the chronic effects of 606A l)biphenyl-4-yl]methyl-5-acetyl-4,5 ,6,7-tetrahydro imidazo[4,5-c]pyridine-4-carboxylic acid disodium salt ), a novel AT(1)-receptor antagonist, on these complications of hypert ension in stroke-prone spontaneously hypertensive rats (SHRSP) using W istar Kyoto rats (WKY) as the control. After 8 weeks treatment from 16 weeks of age with 606A by a subcutaneously implanted osmotic pump, ca rdiac function, cardiac weight, acetylcholine-induced endothelium-depe ndent relaxation in the isolated aorta and renal function were estimat ed. Furthermore, wall thickness of the left ventricle was studied morp hologically. 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 i n SHRSP. Long-term treatments with 606A significantly reduced cardiac weight, left ventricular wall thickness and left ventricular end diast olic pressure, whereas it did not affect cardiac contractility. Endoth elium-dependent relaxation of the aorta was recovered, and total prote in excretion as well as total protein excretion/creatinine excretion r atio was reduced to the level of WKY by the treatment. These results s uggest that 606A not only has a hypotensive effect but also protects c ardiac, renal and vascular tissues from complications of hypertension. Thus, 606A could be an useful drug for treatment of hypertension.