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Related Experiment Videos

New insights into mechanisms underlying nitrate tolerance

T Münzel1, S Kurz, T Heitzer

  • 1Cardiology Division, Department of Medicine, Emory University School of Medicine, Atlanta, Georgia, USA.

The American Journal of Cardiology
|May 30, 1996
PubMed
Summary

Nitrate tolerance, a common issue with organic nitrates, is linked to increased angiotensin II. Blocking angiotensin II pathways can prevent this tolerance, improving vasodilator effectiveness.

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Area of Science:

  • Cardiovascular Pharmacology
  • Vascular Biology

Background:

  • Organic nitrates are vital for treating ischemic conditions but lose efficacy due to nitrate tolerance.
  • The precise mechanisms of nitrate tolerance are not fully understood, but vascular abnormalities are implicated.

Purpose of the Study:

  • To investigate the role of angiotensin II in the development of nitrate tolerance.
  • To explore potential therapeutic strategies to prevent nitrate tolerance.

Main Methods:

  • Experimental observations in vivo and in vitro cell cultures.
  • Assessment of vascular superoxide and endothelin production.
  • Evaluation of nitroglycerin's vasodilator potency under various conditions.
  • Testing the effects of angiotensin-converting enzyme inhibition and angiotensin-I receptor blockade.

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Main Results:

  • Nitrate tolerance is associated with increased vascular superoxide and endothelin production.
  • Angiotensin II mimics vascular changes seen in nitrate tolerance.
  • Concomitant angiotensin-converting enzyme inhibition or angiotensin-I receptor blockade prevents nitrate tolerance and rebound effects.

Conclusions:

  • Elevated angiotensin II levels during nitroglycerin treatment initiate cellular events that attenuate vasodilator effects.
  • Targeting the angiotensin II pathway may be a viable strategy to overcome nitrate tolerance.