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Analytical Techniques for Assaying Nitric Oxide Bioactivity
11:28

Analytical Techniques for Assaying Nitric Oxide Bioactivity

Published on: June 18, 2012

Nitrate tolerance--problems both new and old

J O Parker1

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

The Canadian Journal of Cardiology
|May 1, 1996
PubMed

Insights

Nitrate tolerance rapidly reduces medication effectiveness, impacting treatment. Intermittent dosing preserves therapeutic nitrate effects by allowing washout periods.

Area of Science:

  • Pharmacology
  • Cardiovascular Medicine

Background:

  • Nitrate tolerance is a significant clinical issue, rapidly attenuating therapeutic effects during continuous administration.
  • Understanding the mechanisms of nitrate tolerance is crucial for effective cardiovascular treatment strategies.

Purpose of the Study:

  • To review the current understanding of nitrate tolerance, its mechanisms, and strategies for management.
  • To highlight the clinical significance of nitrate tolerance in daily therapeutic use.

Main Methods:

  • Literature review of studies on nitrate tolerance.
  • Analysis of proposed mechanisms including sulfhydryl depletion, neurohormonal activation, and oxidative stress.
  • Evaluation of clinical strategies to prevent or reverse tolerance.

Main Results:

  • Rapid tolerance develops with oral, transdermal, and intravenous nitrate administration.
  • Proposed mechanisms include sulfhydryl group reduction, neurohormonal activation, plasma volume expansion, and superoxide production.
  • Attempts to prevent tolerance with sulfhydryl donors or other agents have shown limited success.

Conclusions:

  • Nitrate tolerance significantly limits the efficacy of continuous nitrate therapy.
  • Intermittent nitrate dosing, providing washout periods, is an effective strategy to preserve therapeutic benefits.

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