Antihypertensive effect of KB-944, a new calcium antagonist, in conscious normotensive and hypertensive rats.

Hypotensive effect of KB-944 was examined in comparison with diltiazem and nifedipine in normotensive rats, spontaneously hypertensive rats (SHR), renal hypertensive rats and deoxycorticosterone acetate(DOCA)-NaCl hypertensive rats, all in a conscious state. KB-944, diltiazem and nifedipine showed dose-dependent antihypertensive effects in the three different types of hypertensive rats as well as normotensive rats. The relative potency of the test drugs decreased in the following order: nifedipine greater than KB-944 greater than diltiazem. The doses of KB-944 leading to a decrease in systolic blood pressure of 20% of pretreatment level were estimated to be 32.8 mg/kg in normotensive rats, 5.1 mg/kg in SHR, 6.4 mg/kg in renal hypertensive rats and 5.4 mg/kg in DOCA-NaCl hypertensive rats, respectively. The hypotensive effect of KB-944 lasted longer than those of diltiazem or nifedipine. KB-944 and diltiazem increased heart rate in normotensive rats and renal hypertensive rats, though in SHR and DOCA-NaCl hypertensive rats both drugs tended to decrease heart rate. On the other hand, nifedipine increased the heart rate in all types of rats. In SHR, tolerance of KB-944 was not observed with oral administration for 5 weeks at a daily dose of 30 mg/kg.