The
antihypertensive effect of
SD-3211, a structurally novel type of nondihydropyridine
calcium antagonist, was assessed using several types of experimental hypertensive rats.
Oral administration of
SD-3211 (10, 20, and 30 mg/kg) to conscious spontaneously hypertensive rats (SHR),
deoxycorticosterone acetate-
salt hypertensive rats (DHR) and 2-kidney, 1-clip renal hypertensive rats (RHR) resulted in a dose-dependent decrease in systolic blood pressure (SBP). The hypotensive effect of
SD-3211 in these hypertensive rats was more pronounced than in normotensive rats (NR). The potencies of
SD-3211 for the hypotensive effect in the hypertensive rats and NR were 5-7 times greater than that of
diltiazem but 2-3 times less than that of
nicardipine. Furthermore,
SD-3211 showed longer-lasting hypotensive action than
diltiazem and
nicardipine, at the respective equihypotensive dose. During the course of
hypotension,
SD-3211 did not exert any influence on heart rate (HR) in any type of hypertensive rats or NR, in contrast to the appearance of
tachycardia with
nicardipine in SHR, DHR, and NR and of
bradycardia with
diltiazem in DHR. At doses of 10 and 30 mg/kg, the hypotensive doses,
SD-3211 elicited a dose-dependent natriuresis but no kaliuresis in SHR. In the chronic study using SHR,
SD-3211 at 10 mg/kg/day showed an
antihypertensive effect during an administration period of 12 consecutive weeks. These results allow us to conclude that
SD-3211 has a potent and long-lasting hypotensive action with little cardiac effect.