1次高血圧および2次高血圧におけるKv7.4チャネル活動のダウンレギュレーション
Thomas A Jepps1, Preet S Chadha, Alison J Davis
1Division of Biomedical Sciences, St. George's, University of London, United Kingdom.
Circulation
|July 13, 2011
まとめ
電圧誘導のカリウムチャネル (Kv7チャネル) は血管トーンを調節するが,高血圧モデルでは下調調節される. この研究では,高血圧のラットとマウスのKv7チャネル機能を調査し,反応が低下し,Kv7.4タンパク質レベルが低下した.
科学分野:
- 心血管生理学 心血管の生理学
- 分子心臓病学 分子心臓病学
- 薬理学 薬理学とは
背景:
- KCNQ遺伝子 (Kv7チャネル) によってコードされた電圧ゲートされたカリウムチャネルは,血管の血管トーンを調節する重要なレギュレーターです.
- 血管疾患におけるKv7チャネルの機能的影響は,依然としてほとんど不明である.
研究 の 目的:
- 構造的に異なる3つのKv7チャネル活性化剤 (BMS-204352,S-1,およびレチガビン) が,正常血圧および高血圧の動物の血管に及ぼす効果を確かめる.
- 高血圧のモデルにおけるKv7チャネルの機能的影響と発現を調査する.
主な方法:
- 静脈のリラックスと冠動脈の perfusion 試験は,胸部大動脈,中腹動脈のセグメント,および normotensive と自発的に高血圧のラット (SHRs) からLangendorff 心臓製剤を使用して実施されました.
- 隔離されたメゼンテリック動脈の神経細胞のカリウム電流を測定した.
- KCNQ遺伝子とKv7.4タンパク質の発現レベルは,正常血圧と高血圧のラットとマウスの血管組織で分析されました.
主要な成果:
- 3つのKV7活性化剤はすべて,前もって収縮した血管をリラックスさせ,正常血圧の動物における冠動脈 perfusion を増加させた.
- Kv7活性化剤が血管をリラックスさせ,冠動脈の流れを増加させ,K ((+)) 流を増加させる能力は,SHRsとアンジオテンシンIIを注入したマウスの組織において有意に低下していた.
- KCNQ4遺伝子の発現が低下し,Kv7.4タンパク質のレベルは高血圧のネズミとマウスの血管組織で,正常血圧の対照群と比較して有意に低下しました.
結論:
- Kv7チャネルの機能的影響は,2つの異なるラットとマウスの高血圧モデルで劇的に低下しています.
- Kv7.4タンパク質のレベルが低下し,経路機能が低下すると,高血圧における血管機能障害に寄与する.
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