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Related Experiment Videos

Decrease in Ca2+ sensitivity as a mechanism of hydrogen peroxide-induced relaxation of rabbit aorta

T Iesaki1, T Okada, I Shimada

  • 1Department of Internal Medicine, Juntendo University School of Medicine, Tokyo, Japan.

Cardiovascular Research
|May 1, 1996
PubMed
Summary

Hydrogen peroxide (H2O2) increases intracellular calcium in vascular smooth muscle but causes relaxation in phenylephrine-induced contractions. This suggests H2O2 may suppress calcium sensitivity in blood vessels.

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Area of Science:

  • Cardiovascular Physiology
  • Vascular Smooth Muscle Biology
  • Oxidative Stress Research

Background:

  • Hydrogen peroxide (H2O2) exhibits differential effects on vascular smooth muscle, relaxing alpha 1-adrenergic agonist-induced contractions while not affecting high-potassium induced contractions.
  • Understanding the intracellular mechanisms of H2O2 in vascular smooth muscle is crucial for elucidating its physiological and pathological roles.

Purpose of the Study:

  • To investigate the impact of H2O2 on intracellular calcium ([Ca2+]i) levels in vascular smooth muscle.
  • To determine the underlying mechanisms responsible for H2O2-induced relaxation in pre-contracted vascular strips.

Main Methods:

  • Isolated rabbit aortic strips were subjected to isometric contraction using high-potassium or phenylephrine (PE).
  • Intracellular calcium ([Ca2+]i) and tension were measured simultaneously using the fura-2 method following H2O2 administration.

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  • The influence of H2O2 on contractions modulated by protein kinase C activation was also assessed.

    • Main Results:

    • H2O2 caused a reversible increase in [Ca2+]i in vascular smooth muscle under both resting and contracted states.
    • During PE-induced contraction, H2O2 increased [Ca2+]i but decreased muscle tension, indicating relaxation.
    • H2O2 demonstrated a relaxant effect on high-potassium induced contractions when calcium sensitivity was elevated by phorbol 12,13-dibutyrate (PDBu).

    Conclusions:

    • Despite increasing [Ca2+]i, H2O2 induces relaxation in endothelium-denuded, PE-precontracted rabbit aorta.
    • The relaxation mechanism likely involves the suppression of agonist-induced augmentation of calcium sensitivity in the contractile apparatus.