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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

Bioactivation of organic nitrates and the mechanism of nitrate tolerance

Emila Klemenska1, Andrzej Beresewicz

  • 1Department of Clinical Physiology, Medical Centre of Postgraduate Education, Warszawa, Poland.

Cardiology Journal
|January 9, 2009
PubMed

Insights

Organic nitrates treat cardiovascular disease but cause tolerance, reducing effectiveness. Hydralazine may prevent this tolerance and related harmful effects like oxidative stress.

Area of Science:

  • Cardiovascular pharmacology
  • Nitrate drug mechanisms
  • Endothelial function research

Background:

  • Organic nitrates, like nitroglycerin, are vital for cardiovascular disease therapy.
  • Long-term use leads to nitrate tolerance, diminishing drug efficacy.
  • Nitrate tolerance is linked to adverse effects: oxidative stress, endothelial dysfunction, and sympathetic activation.

Purpose of the Study:

  • To review mechanisms of organic nitrate bioactivation and tolerance.
  • To discuss nitrate-induced oxidative stress and endothelial dysfunction.
  • To examine hydralazine's potential role in preventing nitrate tolerance.

Main Methods:

  • Literature review of current concepts.
  • Discussion of biochemical and physiological pathways.
  • Analysis of studies on hydralazine's effects on nitrate tolerance.

Main Results:

  • Organic nitrates require bioactivation for therapeutic effects.
  • Nitrate tolerance involves complex mechanisms, including oxidative stress.
  • Endothelial dysfunction and sympathetic activation are associated with tolerance.
  • Hydralazine shows potential in mitigating nitrate tolerance and dysfunction.

Conclusions:

  • Understanding nitrate bioactivation and tolerance is crucial for effective cardiovascular therapy.
  • Nitrate tolerance is a significant clinical challenge.
  • Hydralazine may offer a strategy to overcome nitrate tolerance and its adverse effects.
  • Further research is needed to fully elucidate hydralazine's protective mechanisms.

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