システミックエンドセリン受容体阻害は,ヒトにおける周周周血管抵抗と血圧を低下させる

W G Haynes¹, C J Ferro, K P O'Kane

¹Department of Medicine, University of Edinburgh, Western General Hospital, UK.

Circulation

|May 15, 1996

まとめ

エンドセリン受容体アンタゴニストであるTAK-044は,健康な男性において血管拡張と低血圧を引き起こした. これは,エンドセリン-1が,血管のトーンと血圧の維持に不可欠であることを示唆しています.

科学分野:

心血管薬理学について
人間の生理学人間生理学

背景:

局所的なエンドセリン-1阻害は血管拡張を引き起こすが,ヒトにおける全身的な効果は不明である.
エンドセリン受容体阻害による全身的心血管効果の調査.

研究の目的:

健康な男性における,強力なエンドセリンのETA/B受容体対抗体であるTAK-044の心臓血管効果を評価する.

主な方法:

2つのランダム化,プラセボ対照,クロスオーバー研究が行われました.
TAK-044を様々な用量 (10-1000 mg) で静脈内投与し,心血管のパラメータを測定した.
エンドセリン-1およびTAK-044輸注に対する前腕血管収縮反応の評価.

主要な成果:

TAK-044は,用量依存の周辺血管拡張と低血圧を引き起こしました.
平均動脈圧の有意な低下と全周回路抵抗の有意な低下が観察されました.
心拍数,心指数,およびプラズマエンドセリン濃度の上昇.

結論:

TAK-044は,外周血管抵抗と血圧を低下させ,循環中のエンドセリンを増加させます.
前腕の血管収縮を外因的なエンドセリン-1に阻害し,血管調節における内因的なエンドセリン-1の役割を示している.
エンドセリン受容体アンタゴニストは,血管拡張剤として潜在的な治療価値を示しています.

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