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.
Nomura
M
M
Department of Pharmacology, Tohoku University, Sendai, Japan.
Kimura
Y
Y
Yoshida
M
M
Satoh
S
S
D000818:Animals; D000959:Antihypertensive Agents; D001794:Blood Pressure / Q000187:drug effects; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D004095:Dihydropyridines / Q000494:pharmacology*; D008297:Male; D051381:Rats; D011918:Rats, Inbred SHR; D011919:Rats, Inbred Strains; D011921:Rats, Inbred WKY
D000959:Antihypertensive Agents; D002121:Calcium Channel Blockers; D004095:Dihydropyridines; C054179:CD 349