葉酸は,ニトログリセリン誘発の酸化窒素合成酵素の機能障害と窒素耐性を予防する:ヒトにおけるin vivo研究
T Gori1, J M Burstein, S Ahmed
1Division of Cardiology, Department of Medicine, Mount Sinai Hospital, and the University of Toronto, Toronto, Canada.
Circulation
|September 6, 2001
まとめ
葉酸サプリメントは,ニトログリセリン誘発の内皮機能不全と健康なボランティアの窒素耐性を予防しました. これは,テトラヒドロビオプテリンの生物利用性が,酸化窒素合成酵素の機能と窒素耐性の鍵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
- 内皮機能の機能について
- 酸化窒素シグナリング
背景:
- 継続的なニトログリセリン (GTN) 治療は,酸化窒素合成酵素 (NOS) の機能を低下させ,おそらくテトラヒドロビオプテリン (BH4) の生物利用性が低下しているためである.
- 葉酸は,様々な疾患状態におけるBH4再生に関与しています.
- GTN誘発のNOS機能障害と耐性を予防する葉酸の役割は,調査が必要です.
研究 の 目的:
- 葉酸の投与がGTN誘発のNOS機能不全を予防するかどうかを調査する.
- 葉酸のサプリメントがGTNに対する耐性の発達を防ぐかどうかを判断する.
主な方法:
- 18人の健康な男性ボランティアの参加によるダブルブラインド・プラセボ対照試験です.
- 参加者は,口服による葉酸 (10 mg/日) またはプラセボを1週間,継続的な経皮GTNと共に投与された.
- 前腕の血流は,血管活性剤に対する反応としてプレチスモグラフィを使用して測定されました.
主要な成果:
- 葉酸投与はGTN誘発の内皮機能不全を予防し,アセチルコリンとN-モノメチル-L-アルギニンに対する反応が保存されたことを証明した.
- 葉酸を投与された被験者は,プラセボ群と比較して,動脈内GTNに対する反応が著しく向上した.
- 葉酸サプリメントは窒素耐性を軽減した.
結論:
- 補足された葉酸は,NOS機能不全と,健康な個人に継続的なGTNによって誘発された窒素耐性を効果的に予防します.
- 減少したBH4生物利用性は,これらの現象における中心的なメカニズムであると仮定されています.
- この発見は,窒素耐性の病原性における酸化ストレスが果たす役割を裏付けている.
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