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Nitroglycerin tolerance: different mechanisms in vascular segments with or without intact endothelial function.

Nicolai Gruhn1, Søren Boesgaard, Claus Andersen

  • 1Medical Department B 2142, Division of Cardiology and Department of Pathology, Copenhagen University Hospital, Rigshospitalet, Blegdamsvej 9, DK-2100 Copenhagen, Denmark. Gruhn@Heartfailure.dk

Journal of Cardiovascular Pharmacology
|July 20, 2002
PubMed
Summary
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Nitroglycerin tolerance development is not affected by endothelium removal. However, interventions to inhibit tolerance work differently in endothelium-denuded vessels, suggesting endothelial dysfunction impacts treatment efficacy.

Area of Science:

  • Cardiovascular Pharmacology
  • Endothelial Function Research
  • Drug Tolerance Mechanisms

Background:

  • In vivo tolerance to nitroglycerin is linked to increased vascular superoxide anion levels.
  • Endothelial function influences nitroglycerin tolerance; its removal can reverse tolerance in normal vessels.
  • The effect of in vivo endothelial dysfunction on nitroglycerin tolerance remains unexamined.

Purpose of the Study:

  • To investigate how in vivo endothelium denudation impacts the development of in vivo nitroglycerin tolerance.
  • To assess the influence of endothelial integrity on the efficacy of interventions aimed at inhibiting nitroglycerin tolerance.

Main Methods:

  • Conscious rat model with prolonged continuous nitroglycerin infusion.
  • In vivo and ex vivo (myograph experiments) assessment of vascular reactivity to nitroglycerin.

Related Experiment Videos

  • Comparison of endothelium-denuded versus endothelium-intact arteries.

    • Main Results:

    • In vivo endothelium denudation did not alter the degree of nitroglycerin tolerance development.
    • Superoxide dismutase and losartan significantly inhibited tolerance in endothelium-intact vessels but not in denuded segments.
    • Interventions showed reduced efficacy in preventing tolerance in endothelium-denuded arteries compared to intact ones.

    Conclusions:

    • The presence or absence of in vivo dysfunctional endothelium significantly alters the effectiveness of interventions targeting nitroglycerin tolerance.
    • Endothelial integrity is crucial for the success of pharmacological strategies aimed at mitigating nitroglycerin tolerance.