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Analytical Techniques for Assaying Nitric Oxide Bioactivity
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Analytical Techniques for Assaying Nitric Oxide Bioactivity

Published on: June 18, 2012

Possible mechanisms of nitrate tolerance

U Elkayam1, A Mehra, A Shotan

  • 1Department of Medicine, University of Southern California (USC) Los Angeles 90033.

The American Journal of Cardiology
|November 27, 1992
PubMed

Insights

Tolerance to organic nitrates develops rapidly with prolonged use, reducing their effectiveness in patients with heart conditions. This nitrate tolerance is dose- and time-dependent, with several potential underlying mechanisms.

Area of Science:

  • Pharmacology
  • Cardiovascular Medicine

Background:

  • Organic nitrates are widely used for treating ischemic heart disease and congestive heart failure.
  • Prolonged exposure to organic nitrates can lead to tolerance, diminishing their therapeutic effects.

Purpose of the Study:

  • To summarize the phenomenon of nitrate tolerance.
  • To discuss the implications of nitrate tolerance in patients with cardiovascular conditions.
  • To review proposed mechanisms underlying nitrate tolerance.

Main Methods:

  • Literature review of studies on organic nitrates and tolerance.
  • Analysis of clinical and preclinical data regarding nitrate efficacy and tolerance development.

Main Results:

  • Nitrate tolerance develops rapidly and affects both peripheral and coronary vasodilation.
  • Tolerance is dose- and time-dependent, attenuating hemodynamic and anti-ischemic effects.
  • Proposed mechanisms include sulfhydryl depletion, increased blood volume, and neurohormonal activation.

Conclusions:

  • Nitrate tolerance is a significant clinical issue in patients with ischemic heart disease and heart failure.
  • Understanding the mechanisms of tolerance is crucial for optimizing nitrate therapy.
  • Further research is needed to mitigate or overcome nitrate tolerance.

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