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Measuring Nitrite and Nitrate, Metabolites in the Nitric Oxide Pathway, in Biological Materials using the Chemiluminescence Method
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Nitrate tolerance--can it be prevented?

J O Parker1

  • 1Department of Medicine, Queen's University, Kingston, Ontario, Canada.

European Heart Journal
|May 1, 1991
PubMed

Insights

Tolerance to organic nitrates, particularly with continuous dosing, can be overcome. Intermittent therapy or controlled-release formulations, like isosorbide-5-mononitrate, prevent nitrate tolerance by allowing washout periods.

Area of Science:

  • Pharmacology
  • Cardiovascular Medicine

Background:

  • Organic nitrates are widely used for angina treatment.
  • Tolerance to organic nitrates can develop during continuous therapy, diminishing their effectiveness.
  • The exact mechanisms underlying nitrate tolerance are not fully elucidated.

Purpose of the Study:

  • To explore the phenomenon of nitrate tolerance in cardiovascular therapy.
  • To investigate the mechanisms potentially involved in nitrate tolerance.
  • To evaluate strategies for preventing or overcoming nitrate tolerance.

Main Methods:

  • Assessing hemodynamic, anti-anginal, and anti-ischemic effects during nitrate therapy.
  • Investigating potential mechanisms including sulfhydryl group depletion and counter-regulatory responses.
  • Evaluating intermittent nitrate therapy and controlled-release formulations.

Main Results:

  • Tolerance to organic nitrates is a recognized clinical issue, especially with 24-hour dosing regimens.
  • Potential mechanisms include reduced nitric oxide production and activation of counter-regulatory systems.
  • Intermittent nitrate therapy and controlled-release formulations appear to prevent tolerance.

Conclusions:

  • Nitrate tolerance can significantly impact therapeutic efficacy.
  • Understanding the mechanisms is crucial for optimizing nitrate therapy.
  • Intermittent dosing or controlled-release formulations are effective strategies to avoid tolerance and maintain therapeutic benefits.

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