Mediators Involved in Decreasing Peripheral Vascular Resistance With Carbachol in the Rat Hind Limb Perfusion Model
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概要
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We examined the involvement of nitric oxide (NO) and/or endothelium-derived hyperpolarizing factor (EDHF) in decreasing peripheral vascular resistance in the rat hind limb perfusion model and analyzed the identity of EDHF in this model. The potency of carbachol (CCh) to produce relaxation was quantitatively similar to sodium nitroprusside (SNP). CCh-induced relaxation was abolished after endothelial denudation, but resistant to nitroarginine and indomethacin. The relaxation was inhibited by tetraethylammonium, ouabain, charybdotoxin plus apamin, and under depolarization. SNP-induced relaxation was accompanied by increased cGMP production, which was inhibited by ODQ (1H-[1,2,4]oxadiazolo[4,3-a]quinoxaline-l-one). Although CCh produced a similar extent of relaxation to SNP, the cGMP level was 24 times lower than that with SNP. Low KCl produced a definite relaxation, which was inhibited by ouabain, but independent of NO, prostacyclin, and endothelium. 1-EBIO (1-ethyl-2-benzimidazolinone) as an activator of IKCa channel also produced a concentration-dependent relaxation, which was inhibited by charybdotoxin, ouabain, and depolarization, but independent of NO and prostacyclin. Clotrimazole and 17-octadecynoic acid as inhibitors of P450 monooxygenase inhibited the CCh-induced relaxation. Meanwhile, catalase at a concentration sufficient to inhibit H2O2-induced relaxation did not exert definite inhibition of the CCh-induced relaxation. These results suggest that CCh produces an endothelium-dependent, EDHF-dependent, and NO-cGMP-independent relaxation and that K+ and metabolite(s) of P450 monooxygenase possibly play an important role for this relaxation.
- 社団法人 日本薬理学会の論文
- 2005-07-20
著者
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AZUMA HIROSHI
Department of Botany, Graduate School of Science, Kyoto University
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Takahashi Ryoko
Department Of Cardiology Hiratsuka Kyosai Heart Center
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Azuma Hiroshi
Department Of Biosystem Regulation Institute Of Biomaterials And Bioengineering Graduate School
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Sakamoto Shuichi
Department of Comprehensive Reproductive Medicine, Tokyo Medical and Dental University
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Aso Takeshi
Department of Comprehensive Reproductive Medicine, Tokyo Medical and Dental University
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LOYAGA-RENDON Renzo
Department of Comprehensive Reproductive Medicine, Graduate School, Tokyo Medical & Dental Universit
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IWASAKI KURASHIGE
Department of Biosystem Regulation, Institute of Biomaterials & Bioengineering, Graduate School, Tok
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Loyaga Renzo
Department Of Comprehensive Reproductive Medicine Graduate School Tokyo Medical & Dental Univers
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Sakamoto Shuichi
Department Of Comprehensive Reproductive Medicine Tokyo Medical And Dental University
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Aso Takeshi
Department Of Comprehensive Reproductive Medicine Tokyo Medical And Dental University
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Aso Takeshi
Department Of Comprehensive Reproductive Medicine Graduate School Tokyo Medical And Dental Universit
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Iwasaki Kurashige
Department Of Biosystem Regulation Institute Of Biomaterials & Bioengineering Graduate School To
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Azuma Hiroshi
Department Of Biosystem Regulation Tokyo Medical And Dental University
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Azuma Hiroshi
Department Of Biosystem Regulation Institute Of Biomaterials And Bioengineering
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Takahashi Ryoko
Department Of Biosystem Regulation Institute Of Biomaterials & Bioengineering Graduate School To
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