Effect of the Intracellular Calcium Antagonist HA1004 on Cerebral Blood Flow in Rats

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The effect of a novel intracellular calcium antagonist, HA1004, on local cerebral blood flow (LCBF) was examined in rats. LCBF was measured in the striatum by the hydrogen clearance method. In the control rats, HA1004 (10 mg/kg, intravenously: IV) increased striatal LCBF by a maximum of 26% despite a transient drop in mean arterial blood pressure (MABP). The LCBF increased for a period of over 100 minutes after the infusion of HA1004. Nicardipine, a calcium entry blocker (0.1 mg/kg, IV), caused a decrease in MABP similar to that induced by HAl004 and increased LCBF by a maximum of 13% for up to 90 minutes after injection. In a second group of rats, the middle cerebral artery (MCA) was occluded by direct ligature of its proximal portion. After MCA occlusion, the LCBF rapidly dropped to 30% of the control value and gradually recovered to the control level during the next 60minutes. However, in rats prophylactically treated with a small dose of HA1004 (1 mg/kg, IV), LCBF recovered more quickly than in untreated rats. The results of this study suggest that HA1004 increases LCBF by enhancing collateral blood flow to ischemic regions and may be useful for the treatment of ischemia.
1988-07-15