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Nitroglycerin reduces myocardial oxygen consumption during exercise despite vascular tolerance
Robert Parent1, Normand Leblanc, Michel Lavallée
1Department of Physiology, Faculty of Medicine, Université de Montréal, Québec, Canada.
American Journal of Physiology. Heart and Circulatory Physiology
|November 8, 2005
Summary
Nitroglycerin (NTG) reduces cardiac oxygen use during exercise, even with tolerance. However, this therapy impairs the body's natural nitric oxide (NO) regulation of oxygen consumption.
Area of Science:
- Cardiovascular Physiology
- Pharmacology
- Nitric Oxide Biology
Background:
- Nitroglycerin (NTG) therapy benefits are limited by vascular tolerance and endothelial dysfunction.
- Nitrate tolerance may affect myocardial oxygen consumption (MV(O2)) and endogenous nitric oxide (NO) modulation during exercise.
Purpose of the Study:
- To determine if nitrate tolerance affects NTG's impact on MV(O2) during exercise.
- To investigate the role of endogenous NO in modulating MV(O2) under NTG tolerance.
Main Methods:
- Chronically instrumented dogs (n=8) underwent hemodynamic and MV(O2) measurements during treadmill exercise.
- Measurements were taken before NTG, during tolerance (3 and 7 days), and after NTG withdrawal.
- Vascular responses to NTG boluses and NO blockade effects on MV(O2) were assessed.
Main Results:
- NTG therapy reduced MV(O2)-triple product (TP) relations, indicating decreased cardiac oxygen demand.
- Despite significant vascular tolerance (>75% reduction in coronary blood flow response), MV(O2) remained reduced.
- NTG-induced MV(O2) reduction and vascular tolerance were reversible upon NTG withdrawal.
- Endogenous NO-dependent modulation of MV(O2) was impaired during NTG tolerance and remained so after withdrawal.
Conclusions:
- NTG sustains reduced cardiac MV(O2) during exercise, independent of metabolic demand, even with coronary microcirculation tolerance.
- NTG withdrawal reverses vascular tolerance and MV(O2) reduction.
- Long-term NTG therapy severely impairs endogenous NO-mediated regulation of myocardial oxygen consumption.