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Related Experiment Videos

Vascular and hemodynamic differences between organic nitrates and nitrites

J A Bauer1, T Nolan, H L Fung

  • 1Department of Pharmaceutics, School of Pharmacy, State University of New York, Buffalo, USA.

The Journal of Pharmacology and Experimental Therapeutics
|January 1, 1997
PubMed
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Organic nitrates like nitroglycerin and organic nitrites such as isoamyl nitrite have different pharmacological actions. Organic nitrites show sustained hemodynamic effects in rats, suggesting potential cardiovascular therapeutic advantages over nitrates.

Area of Science:

  • Pharmacology
  • Cardiovascular Medicine
  • Nitric Oxide Signaling

Background:

  • Organic nitrates and nitrites share similar structures and a nitric oxide-mediated vascular relaxation mechanism.
  • Previous assumptions suggested identical pharmacologic actions for both compound classes.
  • Recent findings indicate distinct vascular enzymes for nitric oxide generation from nitrates versus nitrites.

Purpose of the Study:

  • To investigate the differences in in vitro vascular actions, in vivo hemodynamic effects, and tolerance properties between organic nitrates and nitrites.
  • To test the hypothesis that distinct enzymes lead to divergent pharmacological profiles.
  • To compare the therapeutic potential of organic nitrites against organic nitrates in cardiovascular conditions.

Main Methods:

Related Experiment Videos

  • Isolated blood vessel studies to assess relaxation effects and in vitro tolerance.
  • In vivo hemodynamic studies in rats with congestive heart failure.
  • Comparison of left ventricular end-diastolic pressure changes during continuous infusions of nitroglycerin and isoamyl nitrite.

    • Main Results:

    • Nitroglycerin (NTG) demonstrated more stable relaxation and greater in vitro vascular tolerance compared to isoamyl nitrite (ISAN).
    • Continuous NTG infusion in rats led to tolerance development within 10 hours, with hemodynamic effects returning to baseline.
    • Continuous organic nitrite infusions (isobutyl nitrite and isoamyl nitrite) maintained hemodynamic effects for up to 22 hours, indicating resistance to tolerance.

    Conclusions:

    • Organic nitrites and organic nitrates are not pharmacologically identical, both in vitro and in vivo.
    • Organic nitrites exhibit sustained hemodynamic effects and reduced tolerance development compared to organic nitrates.
    • These findings suggest a potential therapeutic advantage for organic nitrites in treating cardiovascular diseases.