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Using spontaneously hypertensive rats (SHR), we studied the effects of a new calcium antagonist, (+/-)-(R*)-3-[(R*)-1-benzyl-3-piperidyl] methyl 1,4-dihydro-2,6-dimethyl-4-(m-nitrophenyl)-3,5-pyridinedicarboxylate hydrochloride (KW-3049) on the development of hypertension and cardiac hypertrophy. When KW-3049 was administered orally to 5-week-old SHR, a stage before the onset of hypertension, for 12 consecutive weeks, it showed a dose-dependent and marked antihypertensive action. Administration of 3 mg/kg of KW-3049, once a day, significantly suppressed the rise in blood pressure to a similar extent to 15 mg/kg of nicardipine, twice a day. After 12 weeks of administration, the heart weight was decreased or tended to be decreased. Co-administration with propranolol markedly decreased the heart rate, but little affected the heart weight, suggesting changes in the heart rate during the long-term administration of KW-3049 did not largely affect cardiac hypertrophy. KW-3049 did not increase plasma renin activity (PRA) or plasma aldosterone concentration (PAC). There was no significant change in the myocardial DNA and RNA contents. These results suggest the clinical usefulness of KW-3049 as an antihypertensive drug.

journal of toxicological sciences

EFFECT OF THE NEW CALCIUM ANTAGONIST (±)-(R&lt;SUP&gt;*&lt;/SUP&gt;)-3-[(R&lt;SUP&gt;*&lt;/SUP&gt;)-1-BENZYL-3-PIPERIDYL] METHYL 1, 4-DIHYDRO-2, 6-DIMETHYL-4-(m-NITROPHENYL)-3, 5-PYRIDINEDICARBOXYLATE HYDROCHLORIDE (KW-3049) ON CARDIAC HYPERTROPHY IN SPONTANEOUSLY HYPERTENSIVE RATS