Protective Effects of KW-3635, a Thromboxane A2 Antagonist, on Arachidonic Acid-Induced Transient Cerebral Ischemia in Dogs.
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概要
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We investigated the effect of KW-3635, a selective thromboxane (TX) A<SUB>2</SUB>-receptor antagonist, on the arachidonic acid (AA)-induced transient cerebral ischemia in anesthetized dogs. Intracarotid-arterial injection of AA (0.25-1 mg/kg) produced a transient and reversible decrease in electroencephalographic (EEG) activity. The reduction of EEG power was inhibited by the intravenous injection of KW-3635 or aspirin, a cyclooxygenase inhibitor. Local cortical perfusion (LCP) measured by a laser-doppler flow meter was also reduced concomitantly with the reduction of EEG power. Although KW-3635 at 1 and 3 mg/kg (i.v.) did not affect the maximum reduction of LCP, the duration of the reduction period of LCP was significantly shortened by KW-3635. On the other hand, aspirin at 1 and 3 mg/kg (i.v.) inhibited both the maximum and the delay of LCP reduction. The intravenous administration of KW-3635 or aspirin caused dose-dependent inhibition of ex vivo platelet aggregation stimulated by AA (150 μM) at the doses that improve the EEG activity. These data suggest that TXA<SUB>2</SUB> is one of the important factors in the AA-induced transient reduction of EEG activity in anesthetized dogs. The TXA<SUB>2</SUB>-receptor antagonist may be useful for protection against the ischemic brain damage following transient ischemic attack.
- 公益社団法人 日本薬理学会の論文
著者
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HIGO Katsuya
Department of Pharmacology, Pharmaceutical Research Laboratories, Kyowa Hakko Kogyo Co., Ltd.
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Karasawa Akira
Deparment Of Pharmacology Pharmaceutical Research Laboratories Kyowa Hakko Kogyo Co. Ltd.
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Kobayashi Toshiaki
Department Of Applied Physics And Chemistry The University Of Electro-communications
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Satoh Hiroyuki
Department Of Biology Faculty Of Science Toho University
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Kobayashi Toshiaki
Department of Pharmacology, Pharmaceutical Research Laboratories, Kyowa Hakko Kogyo Co., Ltd.,
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