Effects of DX-9065a, an Inhibitor of Factor Xa, on Ellagic Acid-Induced Plantar Skin Thrombosis Assessed in Tetrodotoxin- and N^ω -Nitro-L-Arginine- Treated Rats
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概要
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Effects of DX-9065a ((+)-2S-2-[4-[[(3S)-1-acetimidoyl-3-pyrrolidinyl]oxy]phenyl]-3-[7-amidino-2-naphthyl]propanoic acid hydrochloride pentahydrate), a dibasic propanoic acid and an inhibitor of factor Xa, were compared with those of argatroban, a low molecular weight thrombin inhibitor, on the ellagic acid-induced plantar skin thrombosis in the rats treated with tetrodotoxin and Nω-nitro-<sc>L</sc>-arginine. Plantar skin blood flow was measured with laser Doppler flow meters, and skin temperature of the hindlimb was monitored simultaneously. In order to induce thrombus in plantar skin vasculature, ellagic acid (300 μg, i.a.) was injected into a branch of femoral artery. The formation of thrombus in femoral and plantar vessels was assessed by light microscopy. Ellagic acid decreased plantar skin blood flow and skin temperature. Intravenous injections of DX-9065a (3 mg/kg) and argatroban (1 – 3 mg/kg) significantly inhibited the ellagic acid-induced disturbance of plantar skin blood flow and lowering skin temperature without affecting bleeding time. The oral administration of DX-9065a (30 – 100 mg/kg) significantly prevented the decrease in skin temperature induced by ellagic acid, but it partially inhibited the disturbance of plantar skin blood flow. DX-9065a and argatroban also prolonged prothrombin time in a dose-dependent manner. These results suggest that DX-9065a effectively prevented thrombosis produced by ellagic acid in the skin circulation without a risk of bleeding.
- 社団法人 日本薬理学会の論文
- 2003-04-01
著者
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Ishii Kunio
Department Of Pharmacology Faculty Of Pharmaceutical Sciences University Of Shizuoka
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Chino Daisuke
Department Of Pharmacology And Pharmacotherapy School Of Medicinal Pharmaceutical Sciences Nihon Pha
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Nakayama Koichi
Department Of Molecular And Cellular Pharmacology Faculty Of Pharmaceutical Sciences Iwate Medical U
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FUJITA Yukiyoshi
Department of Pharmacy, The Gunma University Hospital, Gunma University School of Medicine
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Nakayama K
Department Of Pharmacology Faculty Of Pharmaceutical Sciences University Of Shizuoka
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Ishii Kunio
Department Of Molecular Pharmacology Kitasato University School Of Pharmaceutical Sciences
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Fujita Yukiyoshi
Department Of Pharmacology Faculty Of Pharmaceutical Sciences University Of Shizuoka
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Nakayama Koichi
Department Of Cellular And Molecular Pharmacology Graduate School Of Pharmaceutical Sciences Univers
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Chino Daisuke
Department of Chemical Pharmacology, Toho University School of Pharmaceutical Sciences
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