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Vitamin E deficiency accelerates nitrate tolerance via a decrease in cardiac P450 expression and increased oxidative

Yukiko Minamiyama1, Shigekazu Takemura, Seikan Hai

  • 1Department of Food and Health Science, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University, Shikata-cho, Japan. yukiko-m@md.okayama-u.ac.jp

Free Radical Biology & Medicine
|March 8, 2006
PubMed
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Vitamin E supplementation helps prevent nitrate tolerance by reducing oxidative stress and improving the NO/cGMP pathway. Vitamin E deficiency accelerates nitrate tolerance, impacting P450 expression and free radical generation.

Area of Science:

  • Biochemistry
  • Pharmacology
  • Cardiovascular Research

Background:

  • Organic nitrates, like nitroglycerin (NTG), are used for angina but their tolerance mechanisms are unclear.
  • Antioxidants, such as vitamin E, may mitigate nitrate tolerance.
  • Understanding vitamin E's role is crucial for optimizing nitrate therapy.

Purpose of the Study:

  • To investigate the role of vitamin E in the development of nitrate tolerance.
  • To elucidate the biochemical mechanisms underlying vitamin E's effect on nitrate tolerance.

Main Methods:

  • Continuous nitroglycerin infusion in rats to induce tolerance.
  • Assessment of vitamin E levels, blood pressure response to NTG, cardiac P450 expression (CYP1A2), oxidative stress markers (superoxide, lipid peroxidation), and the NO-cGMP pathway (VASP phosphorylation).

Related Experiment Videos

  • Comparison between vitamin E-supplemented, vitamin E-deficient, and control groups.

    • Main Results:

    • Continuous NTG infusion induced tolerance and depleted vitamin E in rats.
    • Vitamin E supplementation inhibited nitrate tolerance, attenuated P450 decrease, and reduced oxidative stress.
    • Vitamin E deficiency exacerbated tolerance by increasing oxidative stress and impairing the NO/cGMP pathway.

    Conclusions:

    • Continuous NTG infusion leads to vitamin E depletion and nitrate tolerance.
    • Vitamin E deficiency accelerates nitrate tolerance through increased oxidative stress, reduced P450 bioconversion, and impaired NO/cGMP signaling.
    • Vitamin E supplementation is a potential strategy to prevent or reduce nitrate tolerance.