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Related Experiment Videos

Nitrate tolerance.

C V Leier

    American Heart Journal
    |July 1, 1985
    PubMed
    Summary
    This summary is machine-generated.

    Nitrate drugs can lose effectiveness over time, a phenomenon known as tolerance, impacting angina and heart failure treatments. Research shows tolerance varies based on drug delivery, but some effects persist in heart failure patients.

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    Area of Science:

    • Pharmacology
    • Cardiovascular Medicine

    Background:

    • Nitrate drugs are widely used for angina and congestive heart failure.
    • Nitrate tolerance, characterized by reduced drug efficacy, is a concern in long-term therapy.
    • Existing research on nitrate tolerance presents conflicting findings.

    Purpose of the Study:

    • To investigate the development of nitrate tolerance in patients with angina pectoris and congestive heart failure.
    • To examine the influence of pharmaceutical and pharmacokinetic factors on nitrate tolerance.
    • To assess the effects of long-term isosorbide dinitrate administration on cardiovascular parameters in heart failure.

    Main Methods:

    • Review of well-designed and controlled studies on nitrate tolerance in angina.
    • Analysis of studies investigating nitrate tolerance in congestive heart failure, focusing on isosorbide dinitrate (40 mg orally every 6 hours) over 3 months.

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  • Comparison of exercise tolerance in heart failure patients receiving long-term isosorbide dinitrate versus placebo.

    • Main Results:

    • Long-term nitrate dosing in angina can lead to tolerance, manifesting as a shorter duration of action or reduced intensity of effect.
    • In heart failure, tolerance to the systemic arterial-vasodilating effects of isosorbide dinitrate developed after 3 months.
    • Pulmonary vascular and venous dilative effects of isosorbide dinitrate were maintained, and exercise tolerance improved in heart failure patients.
    • The leading hypothesis for nitrate tolerance involves altered disposition of reduced sulfhydryl groups.

    Conclusions:

    • Nitrate tolerance is a clinically relevant phenomenon in both angina and heart failure, though its expression may differ.
    • Specific dosing regimens and routes of administration influence the degree of nitrate tolerance.
    • Isosorbide dinitrate, even with systemic tolerance, may retain therapeutic benefits in heart failure, such as improved exercise capacity.