安定した胸の痛みを持つ患者の血小板における窒素耐性
Y Y Chirkov1, A S Holmes, L P Chirkova
1Department of Cardiology, The Queen Elizabeth Hospital, University of Adelaide, Australia.
Circulation
|July 14, 1999
まとめ
安定したアンギナ患者の血小板は,ニトログリセリンやナトリウムニトロプロシドのような酸化窒素ドナーに対する反応が低下しています. この血小板機能の障害は,ガニラートサイクラースの感受性低下と超酸化物濃度の上昇に起因する可能性があります.
科学分野:
- 心血管科学の研究について
- 血小板生理学について
- 酸化窒素シグナリング
背景:
- ニートレジスタンス (Nitrate resistance) は心不全において知られている.
- ニットレート (ニトログリセリンとナトリウムニトロプロシド) に対する血小板反応の減少という同様の現象は,安定した胸痛 (SAP) の患者でも観察されました.
研究 の 目的:
- 安定した心筋梗塞 (SAP) の患者で,酸化窒素 (NO) ドナーに対する血小板の反応の低下を調査する.
- この現象に寄与する根底にあるメカニズム,グアニラートサイクラースの感受性および酸化ストレスを含むことを調査する.
主な方法:
- NOドナー (ニトログリセリンとナトリウムニトロプロシド) がアデノシン・ディフォスファートに誘発された血小板凝集と血小板内循環グアナシンモノフォスファート (cGMP) レベルに及ぼす影響を研究した.
- NOシグナル伝達と酸化ストレスの役割を評価するために,ODQ,グアニラートサイクラース阻害剤,およびスーパーオキシードジスミュータゼ/カタラゼを使用しました.
- 正常な被験者 (n=32) とSAP患者 (n=56) の血液サンプルにおける応答の比較.
主要な成果:
- ニトログリセリンとナトリウムニトロプロシドは,SAP患者の血小板集積とcGMP上昇を正常な被験者と比較して,著しく抑制することが示されました.
- SAP患者からの血小板は,NOドナーに対する感受性の低下を示し,ODQによる抑制があまり顕著でないことが示されました.
- 超酸化物 (O2-) の濃度の上昇がSAP患者の血液で発見され,超酸化物ディスミュータゼは血小板の集積を抑制し,これらの患者でSNPの抗集積効果を高めました.
結論:
- SAP患者の血小板は,NOドナーの抗集積作用とcGMP刺激作用に対して反応が弱い.
- この反応性の低下は,グアニラートサイクラースのNOに対する感受性の低下と,スーパーオキシドによるNO不活性化による可能性がある.
- エンドゲンなNO (EDRF) の抗血小板活性が低下すると,胸痛で血小板の過剰集積に寄与する可能性があります.
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