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Related Experiment Videos

Explaining the phenomenon of nitrate tolerance.

Thomas Münzel1, Andreas Daiber, Alexander Mülsch

  • 1Johannes Gutenberg Universität, II. Medizinische Klinik und Poliklinik, Kardiologie, Mainz, Germany. tmuenzel@uni-mainz.de

Circulation Research
|October 1, 2005
PubMed
Summary

Nitroglycerin tolerance develops due to increased oxidative stress and impaired drug activation. These mechanisms explain reduced effectiveness and potential side effects of this common antianginal agent.

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Area of Science:

  • Pharmacology
  • Cardiovascular Medicine
  • Biochemistry

Background:

  • Nitroglycerin is a primary anti-ischemic and antianginal medication.
  • Continuous nitroglycerin use leads to diminished therapeutic efficacy, known as tolerance.
  • Tolerance involves pseudotolerance and long-term vascular changes, including loss of responsiveness.

Purpose of the Study:

  • To review the mechanisms underlying nitroglycerin tolerance.
  • To elucidate the roles of oxidative stress and impaired drug bioactivation.
  • To present a unified concept for nitroglycerin and cross-tolerance.

Main Methods:

  • Literature review of studies on nitroglycerin tolerance.
  • Analysis of biochemical pathways involved in nitroglycerin metabolism and action.

Related Experiment Videos

  • Examination of the role of reactive oxygen species and mitochondrial function.

    • Main Results:

    • Nitroglycerin tolerance stems from increased vascular superoxide production and protein kinase C activation.
    • Superoxide formation leads to peroxynitrite, impairing nitric oxide signaling and enzyme function.
    • A novel mechanism involves inhibition of mitochondrial aldehyde dehydrogenase, crucial for nitroglycerin bioactivation.

    Conclusions:

    • Nitroglycerin tolerance is driven by both increased oxidative stress and impaired bioactivation.
    • Mitochondria are identified as both a source of reactive oxygen species and a target for tolerance development.
    • Understanding these mechanisms offers insights into endothelial dysfunction and potential therapeutic strategies.