Effects of a New Dihydropyridine Derivative, FRC-8653, on Blood Pressure in Conscious Spontaneously Hypertensive Rats

Antihypertensive effects of FRC-8653, a new 1, 4-dihydropyridine derivative, and its combined effects with an angiotensin converting enzyme (ACE) inhibitor, a diuretic, and a β-adrenergic blocking agent were examined in conscious spontaneously hypertensive rats (SHR). When administered intravenously to SHR (10, 30μg/kg), FRC-8653 lowered blood pressure more slowly and sustained it longer than nifedipine and nicardipine. Consecutive once-daily administrations of FRC-8653 to SHR (3 mg/kg, p.o.) produced a stable reduction of blood pressure throughout the experimental period of 29 d. When blood pressure was continuously measured for 24 h in conscious unrestricted SHR, orally administered FRC-8653 produced a long-lasting reduction in blood pressure. When concomitantly used with atenolol (30 mg/kg, p.o.), the antihypertensive effect of FRC-8653 was augmented in both potency and duration. However, simultaneous administration of captopril (30 mg/kg, p.o.) or hydrochlorothiazide (2.5 mg/kg, p.o.) did not modify the antihypertensive effect of FRC-8653.