Antihypertensive effect of a new dihydropyridine calcium entry blocker in conscious hypertensive and normotensive rats.

The antihypertensive effects of orally administered CD-349, (2-nitratopropyl-3-nitratopropyl-2,6-dimethyl-4-(3-nitrophen yl)- 1,4-dihydropyridine-3,5-dicarboxylate), a new dihydropyridine calcium-entry blocker, were evaluated in comparison with nifedipine in spontaneously hypertensive rats (SHR), renal hypertensive rats (RHR) and normotensive rats (NTR) all in a conscious state. CD-349 (0.3, 1.0 and 3.0 mg/kg) and nifedipine (1.0 mg/kg) produced a long-lasting decrease in mean arterial blood pressure (BP) and an increase in heart rate (HR) in all the rat groups; the effects of CD-349 were dose-dependent and greater in hypertensive rats than in NTR. As compared with nifedipine at the same dose of 1 mg/kg, the hypotensive effect of CD-349 was relatively slower in onset and longer-lasting, thereby suggesting that gastrointestinal absorption of CD-349 was slower than that of nifedipine. The increase in HR associated with the hypotension induced by CD-349 at 1 mg/kg was relatively transient in comparison with that induced by nifedipine at the same dose in both types of hypertensive rat. From these results, it is expected that CD-349 could be a useful antihypertensive drug.