人間とヒト以外の霊長類におけるナイトライト注入:内分泌系効果,薬理動力学,耐性形成
André Dejam1, Christian J Hunter, Carole Tremonti
1Molecular Medicine Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
Circulation
|September 26, 2007
まとめ
ニトリットは強力な血管拡張剤と酸化窒素 (NO) の貯蔵庫として作用し,血管機能とNOの恒常性を調節します. この研究は,ニートリットを明らかにしています.
科学分野:
- 心血管生理学 心血管の生理学
- エンドクリノロジー エンドクリノロジー
- 薬理学 薬理学とは
背景:
- 生理学的濃度において,血管拡張剤およびシグナル伝達分子としてのナイトライトの役割は認められています.
- 低毒性血管拡張と窒素酸塩の効果への潜在的な貢献が示唆されています.
- ナイトライトの効能,運動,メカニズム,耐性に関する重要な疑問は依然として残っています.
研究 の 目的:
- 血管拡張剤としてのナイトライトの効能,運動,および作用メカニズムを調査する.
- 窒素酸塩が,有機窒素酸塩とは異なり,耐性を誘発するかどうかを判断する.
- 窒素酸化物のホメオスタシスと血管の調節におけるニトリートの役割を明らかにする.
主な方法:
- ヒトのボランティアと非ヒトの霊長類における生化学的,生理学的,および薬理学的研究.
- ナイトライト輸液プロトコルが採用されました.
- 試験されたメカニズムには,キサンチン酸化還元酵素による還元,非酵素的不均衡化,およびデオキシヘモグロビンによる還元が含まれていました.
主要な成果:
- ナイトライトは,生理学的濃度に近い濃度で強力で急速な血管拡張を示した.
- ニトリットは内分泌の酸化窒素貯蔵庫として機能し,遠隔血管拡張を引き起こします.
- ニトリートは,ヘモグロビンとアスコルバートとの血管内反応によって酸化窒素に還元されます.
- ザンチン酸化還元酵素の阻害は,阻害されるのではなく,ナイトライト誘発の血管拡張を強化した.
- 窒素酸塩は,有機窒素酸塩とは対照的に,耐性を誘導しませんでした.
結論:
- ニトリットは,血管機能の生理学的調節体であり,内分泌の窒素酸化物ホメオスタシスの役割を果たします.
- ニトリートは,有機窒素酸塩の活性代謝産物である.
- 窒素酸塩は,有機窒素酸塩に関連する酵素耐性を回避するための治療的可能性を秘めています.
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