アンジオテンシンII型2受容体媒介の血管拡張は,ヒトの冠動脈小動脈で起こります
Wendy W Batenburg1, Ingrid M Garrelds, Catherine Chapuis Bernasconi
1Department of Pharmacology, Erasmus MC, Rotterdam, The Netherlands.
Circulation
|May 1, 2004
まとめ
アンジオテンシンII型2受容体刺激は,ブラジキニンB2受容体と酸化窒素によって媒介されるヒトの冠動脈小動脈の血管拡張を引き起こす. この効果は,高齢者においてより顕著である.
科学分野:
- 心血管生理学 心血管の生理学
- 薬理学 薬理学とは
- 分子生物学は分子生物学である.
背景:
- アニオテンシンII型2 (AT2) 受容体の刺激により,ネズミの冠動脈血管拡張が起こります.
- AT2受容体媒介の血管拡張は,人の大動脈には存在しない.
- 人間の冠動脈小動脈 (HCMA) のAT2受容体の役割は不明である.
研究 の 目的:
- 人間の冠動脈小動脈 (HCMA) のアニオテンシンII (Ang II) 誘発血管拡張を調査する.
- HCMAにおけるAT2受容体媒介効果に関与する受容体経路を決定する.
- AT2受容体の機能に対するドナーの年齢の影響を評価する.
主な方法:
- 49人の心臓弁のドナーのHCMAが使用されました.
- 血管機能の評価は,マルバニーミオグラフを用いて行われました.
- AngII誘発の血管収縮と放松を測定した.
- レセプターアンタゴニスト (イルベサタン,PD123319),酸化窒素合成酵素阻害剤 (L-NAME),ブラジキニンB2受容体アンタゴニスト (Hoe140) が使用されました.
- ラジオリガンド結合とRT-PCRにより,AT2受容体発現が確認されました.
主要な成果:
- Ang IIは,Ang II型1受容体を通して,HCMAの濃度依存の収縮を引き起こした.
- PD123319によるAT2受容体阻害は,Ang II誘発収縮を強化し,AT2受容体の血管拡張作用を示した.
- Ang IIは,Ang II型1受容体がブロックされたときに,前収縮のHCMAでリラックスを誘導した.
- この緩和は,ブラジキニンB2受容体,酸化窒素,内皮に依存していた.
- Ang II誘発の収縮に対するPD123319の強化効果は,ドナーの年齢とともに増加した.
結論:
- AT2受容体媒介の血管拡張は,ヒトの冠動脈小動脈で起こります.
- この血管拡張には,ブラジキニンB2受容体と酸化窒素が関与し,おそらく内皮細胞に作用する.
- AT2受容体が媒介する血管拡張の貢献は,ヒトの年齢とともに増加する.
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