Antihypertensive effects of the new calcium antagonist benidipine hydrochloride in rats.
Using spontaneously hypertensive rats (SHR), DOCA-NaCl hypertensive rats (DHR) and normotensive rats (NTR), the antihypertensive action of (+/-)-(R*)-2,6-dimethyl-4-(m-nitrophenyl)-1,4-dihydropyridine-3,5-dic arb oxylic acid (R*)-1-benzyl-3-piperidinyl ester, methyl ester hydrochloride (benidipine hydrochloride, KW-3049) was comparatively evaluated with those of nicardipine and hydralazine. Administration of KW-3049 at 0.5, 1 and 3 mg/kg (p.o.) showed dose-dependent antihypertensive action. This action appeared gradually and it lasted longer than those of nicardipine and hydralazine. The administration of KW-3049 at 0.5 mg/kg (p.o.) did not show any effect on the blood pressure of NTR, but a long-lasting blood pressure lowering action was observed by the administration at 1 and 3 mg/kg (p.o.). This antihypertensive action specific to the hypertensive animals was similar to that of nicardipine, however, it was different from that of hydralazine, with which the blood pressure in SHR, DHR and NTR was lowered in similar degrees. Also, administration of KW-3049 caused tachycardia concomitant with the fall of blood pressure, however, it was mild as compared with those of nicardipine and hydralazine. When KW-3049 at doses of 3 and 10 mg/kg (p.o.) once a day was continuously administered to SHR for 31 days and changes of the antihypertensive action were observed, no tolerance developed and rebound hypertension following the discontinuation of medication did not occur. When the effect on the urinary volume and electrolyte excretion was evaluated in rats loaded with physiological saline solution, a natriuretic effect was observed by the administration of KW-3049 at 0.5, 1 and 3 mg/kg (p.o.).(ABSTRACT TRUNCATED AT 250 WORDS)
Karasawa
A
A
Pharmaceutical Research Laboratories, Kyowa Hakko Kogyo, Co., Ltd., Shizuoka, Japan.
Kubo
K
K
Shuto
K
K
Oka
T
T
Nakamizo
N
N
D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology* / Q000627:therapeutic use; D001794:Blood Pressure / Q000187:drug effects*; D002121:Calcium Channel Blockers / Q000494:pharmacology* / Q000627:therapeutic use; D055598:Chemical Phenomena; D002621:Chemistry; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D004359:Drug Therapy, Combination; D006339:Heart Rate / Q000187:drug effects*; D006830:Hydralazine / Q000494:pharmacology / Q000627:therapeutic use; D006973:Hypertension / Q000188:drug therapy; D008297:Male; D009529:Nicardipine / Q000494:pharmacology / Q000627:therapeutic use; D009543:Nifedipine / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D051381:Rats; D011918:Rats, Inbred SHR; D011919:Rats, Inbred Strains; D012083:Renin / Q000097:blood; D014554:Urination / Q000187:drug effects
D000959:Antihypertensive Agents; D002121:Calcium Channel Blockers; C050883:benidipine hydrochloride; D006830:Hydralazine; D009529:Nicardipine; D012083:Renin; D009543:Nifedipine