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Phenomenon of nitrate tolerance
1Division of Clinical Pharmacology, University of South Florida.
American Heart Journal
|July 1, 1994
Summary
Nitrate tolerance reduces the effectiveness of vasodilators like nitric oxide (NO) with continuous use. Brief interruptions in nitrate therapy are the best way to prevent or reverse this tolerance.
Area of Science:
- Pharmacology
- Cardiovascular Medicine
Background:
- Therapeutic nitrates act as exogenous sources of nitric oxide (NO), a key mediator of vasodilation.
- Nitrates exhibit vasodilatory and antiplatelet effects that diminish with continuous exposure, leading to nitrate tolerance.
Purpose of the Study:
- To review the phenomenon of nitrate tolerance, its mechanisms, and clinical implications.
- To evaluate strategies for preventing or reversing nitrate tolerance.
Main Methods:
- Review of existing literature on nitrate tolerance.
- Analysis of cellular and systemic processes involved in tolerance development.
- Assessment of clinical evidence for nitrate tolerance and its management.
Main Results:
- Nitrate tolerance occurs with continuous nitrate therapy, affecting vasodilatory and antiplatelet effects.
- The causes of nitrate tolerance are multifactorial, involving both cellular and systemic mechanisms.
- No adjuvant pharmacologic interventions have proven effective in managing nitrate tolerance.
Conclusions:
- Interruption of nitrate exposure for 8-12 hours is the most effective method to prevent or reverse tolerance.
- Despite documented tolerance, some patients may still experience symptom relief and clinical benefit from nitrates.
- The clinical significance of nitrate tolerance remains controversial, necessitating further research into quality-of-life and ischemia relief.