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The antihypertensive effects of AE0047, a novel 1,4-dihydropyridine-type calcium antagonist, were investigated in spontaneously hypertensive rats (SHR/crj) and two kidney-one clip renal hypertensive dogs (RHD). AE0047, which was orally administered at the dose of 0.3, 1 or 3 mg/kg once daily for 8 consecutive weeks to SHR/crj, exhibited a dose-related decrease in systolic blood pressure. The antihypertensive action was reinforced during the drug treatment at 0.3 and 1 mg/kg. At each dose, the trough-to-peak (T/P) ratio was above 0.50 two weeks later. Although the reflex tachycardia was observed at 1 or 3 mg/kg on the 1st day, it gradually weakened within 8 weeks. Long-term treatment with AE0047 led to the regression of left ventricular hypertrophy. Furthermore, AE0047 had no influences on lipid and glucose metabolism. In RHD, and AE0047 capsule (GJ-0956) containing 2 or 8 mg of the drug was administered for 2 weeks. GJ-0956 produced no reduction in blood pressure at 2 mg, but enhanced the antihypertensive effect starting at 8 mg. The T/P ratios were 0.52 and 0.67 for the systolic and diastolic pressure, respectively, on the 14th day. These results indicate that AE0047 may be expected to exhibit beneficial effects for the clinical treatment of hypertension.

Antihypertensive effects of long term treatment with AE0047, a novel long-lasting calcium antagonist, in hypertensive models of rats and dogs.