Vascular α1-Adrenoceptor Subtype Selectivity and α1-Blocker-Induced Orthostatic Hypotension
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概要
- 論文の詳細を見る
Newly developed α1-adrenoceptor antagonists including naftopidil are free from the “prazosin-like” side effect of orthostatic hypotension and associated symptoms. We investigated the mechanism for the differential effects of naftopidil and prazosin on the development of postural hypotension, with special attention on their selectivity for the α1-adrenoceptor subtype. We observed that head-up tilt caused a similar extent of drop in mean arterial pressure in control, naftopidil (1 mg/kg)- or prazosin (10 μg/kg)-treated rats; however, the tilt-induced postural hypotension was recovered within 2 min in the naftopidil-treated group, but not in the prazosin-treated group. Comparing an inhibitory effect on noradrenaline-induced contraction in the rat aorta and portal vein, we found that naftopidil was sixfold less potent in the portal vein, while prazosin showed similar potency in both tissues. Reverse transcription-polymerase chain reaction analysis showed that the expression of α1d-adrenoceptor mRNA predominated in the aorta, while that of α1b-adrenoceptor mRNA predominated in the portal vein. Using cloned rat α1-adrenoceptor subtypes, we found that naftopidil was selective for the α1d-subtype with approximately ninefold higher affinity than at the other subtypes. These results show that the pharmacological character of naftopidil, combined with the differential expression of the α1-adrenoceptor subtype in the artery and the vein, may partly explain the differential effect of naftopidil and prazosin on head-up tilt-induced hemodynamic responses.
- 社団法人 日本薬理学会の論文
- 1998-05-01
著者
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TSUJIMOTO Gozoh
Department of Genomic Drug Discovery Science, Kyoto University Graduate School of Pharmaceutical Sci
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Hirasawa Akira
Department Of Gynecology Keio University Hospital
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AWAJI Takeo
Department of Phamacology, Yamanashi Medical University
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Tsujimoto Gozoh
Department Of Genomic Drug Discovery Science Graduate School Of Pharmaceutical Sciences Kyoto Univer
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Tsujimoto Gozoh
Dep. Of Genomic Drug Discovery Sci. Graduate School Of Pharmaceutical Sciences Kyoto Univ. Jpn
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Tsujimoto Gozoh
Department Of Molecular Cell Pharmacology National Research Institute For Child Health And Developme
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Tsujimoto Gozoh
Department Of Molecular And Cellular Pharmacology National Children's Medical Research Center
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Tsujimoto Gozoh
Department Of Molecular Cell Pharmacology National Children 's Medical Research Center
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Takada Tatsuyuki
Department Of Experimental Radiology Shiga University Of Medical Science
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Takada Tatsuyuki
Department Of Molecular Cell Pharmacology National Children 's Medical Research Center
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Hirasawa Akira
Department Of Molecular Cell Pharmacology National Children 's Medical Research Center
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Hirasawa Akira
Department Of Biophysics And Biochemistry Graduate School Of Science The University Of Tokyo
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Awaji Takeo
Department Of Pharmacology Yamanashi Medical College
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Awaji Takeo
Department Of Molecular Cell Pharmacology National Children 's Medical Research Center
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TAKE Hitoshi
Department of Molecular, Cell Pharmacology, National Children 's Medical Research Center
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SHIBATA Katsushi
Department of Molecular, Cell Pharmacology, National Children 's Medical Research Center
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IKEGAKI Ichiro
First Laboratory for Pharmacological Research, Institute for Life Science Research, Asahi Chemical I
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ASANO Toshio
First Laboratory for Pharmacological Research, Institute for Life Science Research, Asahi Chemical I
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Take Hitoshi
Department Of Molecular Cell Pharmacology National Children 's Medical Research Center
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Ikegaki Ichiro
Institute Of Life Science Research Asahi Kasei Corporation
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Shibata Katsushi
Department Of Molecular Cell Pharmacology National Children 's Medical Research Center
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Tsujimoto Gozoh
Department Of Genomic Drug Discovery Science Graduate School Of Pharmaceutical Sciences Kyoto Univer
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Tsujimoto Gozoh
Department Of Genomic Drug Discovery Science Graduate School Of Pharmaceutical Sciences Kyoto Univer
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Ikegaki Ichiro
Laboratory For Pharmacology Institute For Life Science Research Asahi Chemical Industry
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ASANO Toshio
Laboratory for Pharmacology, Institute for Life Science Research, Asahi Chemical Industry
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