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Prevention of nitroglycerin tolerance with diuretics
N Mohanty1, A G Wasserman, P Walker
1Department of Medicine, George Washington University, Washington, DC 20037, USA.
American Heart Journal
|September 1, 1995
Summary
Diuretics may prevent tolerance to nitroglycerin (NTG) by reducing intravascular expansion. This study found that hydrochlorothiazide maintained NTG
Area of Science:
- Cardiovascular pharmacology
- Clinical investigation
Background:
- Nitroglycerin (NTG) tolerance can develop with prolonged use, potentially due to intravascular volume expansion.
- Preventing NTG tolerance is crucial for sustained therapeutic efficacy.
Purpose of the Study:
- To investigate whether concomitant diuretic use can prevent the development of tolerance to nitroglycerin.
- To test the hypothesis that diuretics mitigate NTG-induced intravascular expansion, thereby preserving venodilator response.
Main Methods:
- A randomized controlled trial involving 23 healthy volunteers.
- Participants received either hydrochlorothiazide or placebo during a 74-hour continuous nitroglycerin (NTG) exposure via patches.
- Venodilator response to NTG was assessed using venous forearm plethysmography at multiple time points.
Main Results:
- Baseline venodilator responses to NTG were comparable between the hydrochlorothiazide and placebo groups.
- After 74 hours of NTG exposure, the placebo group showed significant attenuation in venodilator response (NTG tolerance).
- In contrast, the hydrochlorothiazide group maintained full venodilator activity, indicating prevention of NTG tolerance.
Conclusions:
- Concomitant administration of hydrochlorothiazide appears effective in preventing the development of tolerance to prolonged nitroglycerin therapy.
- Diuretics may counteract the intravascular volume expansion associated with NTG, preserving its therapeutic venodilator effects.
- These findings suggest a potential clinical strategy to enhance the durability of nitroglycerin treatment.