Vascular α1-Adrenoceptor Subtype Selectivity and α1-Blocker-Induced Orthostatic Hypotension

• Take Hitoshi

  Department of Molecular, Cell Pharmacology, National Children’s Medical Research Center

• Shibata Katsushi

  Department of Molecular, Cell Pharmacology, National Children’s Medical Research Center

• Awaji Takeo

  Department of Molecular, Cell Pharmacology, National Children’s Medical Research Center

• Hirasawa Akira

  Department of Molecular, Cell Pharmacology, National Children’s Medical Research Center

• Ikegaki Ichiro

  First Laboratory for Pharmacological Research, Institute for Life Science Research, Asahi Chemical Industry

• Asano Toshio

  First Laboratory for Pharmacological Research, Institute for Life Science Research, Asahi Chemical Industry

• Takada Tatsuyuki

  Department of Molecular, Cell Pharmacology, National Children’s Medical Research Center

• Tsujimoto Gozoh

  Department of Molecular, Cell Pharmacology, National Children’s Medical Research Center

書誌事項

タイトル別名

• Vascular .ALPHA.1-Adrenoceptor Subtype Selectivity and .ALPHA.1-Blocker-Induced Orthostatic Hypotension.
• Vascular アルファ1 Adrenoceptor Subtype Sel
• Vascular a1-adrenoceptor subtype selectivity and a1-blocker induced orthostatic hypotension

抄録

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 α_1d-adrenoceptor mRNA predominated in the aorta, while that of α_1b-adrenoceptor mRNA predominated in the portal vein. Using cloned rat α₁-adrenoceptor subtypes, we found that naftopidil was selective for the α_1d-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.

収録刊行物

• Jpn.J.Pharmacol.

  Jpn.J.Pharmacol. 77 (1), 61-70, 1998

  公益社団法人 日本薬理学会

キーワード

• α<SUB>1</SUB>-Adrenoceptor
• Naftopidil
• Prazosin
• Postural hypotension
• Reverse transcription-polymerase chain reaction

詳細情報

• CRID: 1390001204285311872
• NII論文ID: 10008680181
• NII書誌ID: AA00691188
• DOI: 10.1254/jjp.77.61
• COI: 1:CAS:528:DyaK1cXjsFSktb0%3D
• ISSN: 13473506
• ISSN: 00215198
• NDL書誌ID: 4503675
• PubMed: 9639061
• Web Site: https://ndlsearch.ndl.go.jp/books/R000000004-I4503675
• Web Site: https://api.elsevier.com/content/article/PII:S0021519819311473?httpAccept=text/xml
• Web Site: https://api.elsevier.com/content/article/PII:S0021519819311473?httpAccept=text/plain
• Web Site: https://www.jstage.jst.go.jp/article/jjp/77/1/77_1_61/_pdf
• Web Site: https://search.jamas.or.jp/link/ui/1998210953
• 本文言語コード: en
• データソース種別:
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  • NDL
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  • PubMed
  • CiNii Articles
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