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Related Experiment Videos

Nitrosothiol and nitrate tolerance.

H L Fung, R Poliszczuk

    Zeitschrift Fur Kardiologie
    |January 1, 1986
    PubMed
    Summary
    This summary is machine-generated.

    Nitrate tolerance in rats involves reduced metabolite production, impacting vasodilation. S-nitroso N-acetyl penicillamine may offer a non-tolerance-inducing alternative for treating vascular conditions.

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    Area of Science:

    • Pharmacology
    • Cardiovascular Physiology
    • Biochemistry

    Background:

    • Nitrate tolerance limits the efficacy of nitroglycerin and related drugs.
    • The exact mechanisms underlying nitrate tolerance, particularly the role of metabolites, remain incompletely understood.
    • Intracellular metabolic pathways are believed to precede the vasodilatory effects of nitrates.

    Purpose of the Study:

    • To investigate the role of 1,2-glyceryl dinitrate metabolite production in nitrate tolerance.
    • To explore the vasodilatory properties of S-nitroso N-acetyl penicillamine in nitroglycerin-tolerant blood vessels.
    • To assess the potential of nitrosothiols as therapeutic agents that do not induce tolerance.

    Main Methods:

    • Studies were conducted on Sprague-Dawley rats.

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  • Aortic tissues were analyzed for nitrate metabolite production.
  • Vasodilating properties of S-nitroso N-acetyl penicillamine were tested on tolerant blood vessels.

    • Main Results:

    • Nitrate tolerance in aortic tissues correlated with reduced 1,2-glyceryl dinitrate metabolite production.
    • This suggests impaired vascular metabolism contributes to tolerance.
    • S-nitroso N-acetyl penicillamine maintained vasodilating effects in nitroglycerin-tolerant vessels.

    Conclusions:

    • Reduced vascular metabolism of nitrates, specifically 1,2-glyceryl dinitrate, is linked to nitrate tolerance.
    • The Ignarro Nitrosothiol Hypothesis supports the vasodilatory action of S-nitroso N-acetyl penicillamine.
    • Nitrosothiols warrant further investigation as potential non-tolerance-inducing therapeutic agents.