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Related Experiment Videos

Preserved endothelial function after long-term eccentric isosorbide mononitrate despite moderate nitrate tolerance.

Senta Müller1, Ute Laber, Jost Müllenheim

  • 1Institut für Pharmakologie und Klinische Pharmakologie, Heinrich-Heine-Universität, Moorenstrasse 5, 40225 Duesseldorf, Germany.

Journal of the American College of Cardiology
|June 12, 2003
PubMed
Summary

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Long-term, eccentric isosorbide mononitrate (ISMN) treatment did not increase vascular superoxide production or impair endothelial function, even with moderate nitrate tolerance. This suggests ISMN is unlikely to worsen endothelial dysfunction in coronary artery disease.

Area of Science:

  • Pharmacology
  • Cardiovascular Research
  • Endothelial Function

Background:

  • Continuous transdermal glyceryl trinitrate (GTN) can induce nitrate tolerance linked to increased vascular superoxide and endothelial dysfunction.
  • The effect of eccentric oral nitrate administration on vascular superoxide is not well understood.

Purpose of the Study:

  • To investigate the long-term effects of eccentric oral isosorbide mononitrate (ISMN) on endothelial function.
  • To determine if eccentric ISMN administration leads to increased vascular superoxide production.

Main Methods:

  • Rabbits received placebo, low-dose ISMN (ISMN-2), or high-dose ISMN (ISMN-200) eccentrically, twice daily for four months.
  • Aortic reactivity and superoxide production were assessed after the final ISMN dose.

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Main Results:

  • Eccentric ISMN treatment did not affect aortic reactivity to phenylephrine, acetylcholine, or a nitric oxide donor.
  • Moderate nitrate tolerance developed in the ISMN-200 group, but without increased aortic superoxide production.
  • ISMN plasma levels were dose-dependent.

Conclusions:

  • Long-term, high-dose eccentric ISMN does not increase vascular superoxide or impair endothelium-dependent vasorelaxation.
  • The development of moderate nitrate tolerance with eccentric ISMN is not associated with increased oxidative stress.
  • Eccentric ISMN is unlikely to aggravate endothelial dysfunction in coronary artery disease patients.