スピロノラクトンは,酸化窒素のバイオアクティビティを増加させ,内皮血管拡張器の機能不全を改善し,慢性心不全の患者で血管アンジオテンシンI/アンジオテンシンII変換を抑制します
C A Farquharson1, A D Struthers
1University Department of Clinical Pharmacology and Therapeutics, Ninewells Hospital and Medical School, Dundee, UK. c.a.j.farquharson@dundee.ac.uk
Circulation
|February 15, 2000
まとめ
スピロノラクトンは,心不全患者の内皮機能と血管レニン-アニオテンシン軸の活動を改善します. この研究は,スピロノラクトネの新たなメカニズムを明らかにしています.
科学分野:
- 心臓病学 心臓病学
- 薬理学 薬理学とは
- 血管生物学 血管生物学
背景:
- RALES研究では,慢性心不全におけるスピロノラクトンの死亡率の利点が示されました.
- この研究では,内皮機能の改善または血管内レニン-アニオテンシン軸抑制がスピロノラクトンの利点を説明するかどうかを調査しました.
研究 の 目的:
- スピロノラクトンが内皮機能を改善するという仮説を検証するために.
- 心不全における血管レニン-アニオテンシン軸に対するスピロノラクトンの効果を評価する.
主な方法:
- ランダム化,プラセボ対照,二重盲検のクロスオーバー研究で,NYHAクラスII-IIIの心不全患者10人を対象に実施した.
- アセチルコリンとN-モノメチル-L-アルギニン (L-NMMA) を使用して前腕血管内皮機能を評価しました.
- アンジオテンシンIとIIを用いて血管のACE活性を測定した.
主要な成果:
- スピロノラクトンは,アセチルコリンに対する前腕の血流反応を有意に改善した (P<0.001).
- スピロノラクトンは,L-NMMAに対する血管収縮反応を増加させた (P<0.05).
- スピロノラクトンは,アニオテンシンIに対する血管反応を著しく低下させ (P<0.05),アニオテンシンIIの反応は変化しなかった.
結論:
- スピロノラクトンは,心不全における内皮機能不全と窒素酸化物 (NO) の生物活性を強化します.
- スピロノラクトンは,血管のアンジオテンシンIからIIへの変換を阻害する.
- これらのメカニズムは,心血管疾患による死亡率に対するスピロノラクトンの有益な効果に貢献します.
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