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Related Experiment Videos

Superoxide: a key player in hypertension.

Salvatore Cuzzocrea1, Emanuela Mazzon, Laura Dugo

  • 1Institute of Pharmacology, University of Messina, Italy.

FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology
|January 14, 2004
PubMed
Summary

Superoxide anion contributes to hypertension by reducing nitric oxide (NO) function in spontaneously hypertensive rats. A superoxide dismutase mimetic (M40403) lowered blood pressure by restoring NO availability and improving vascular function.

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Area of Science:

  • Cardiovascular Research
  • Pharmacology
  • Biochemistry

Background:

  • Spontaneously hypertensive rats (SHR) exhibit elevated superoxide levels in the vessel wall.
  • Superoxide is implicated in potentiating endothelium-dependent vasodilation when blocked.
  • The interaction between superoxide and nitric oxide (NO) in hypertension requires further elucidation.

Purpose of the Study:

  • To determine the role of superoxide anion in the development of hypertension.
  • To investigate the interaction between superoxide and nitric oxide (NO) in hypertensive rats.
  • To evaluate the efficacy of a superoxide dismutase mimetic in lowering blood pressure and improving vascular function.

Main Methods:

  • Utilized a synthetic superoxide dismutase mimetic (M40403) to selectively scavenge superoxide anion.

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  • Administered M40403 to spontaneously hypertensive rats (SHR) and Wistar Kyoto (WKY) rats to assess effects on mean arterial pressure (MAP).
  • Investigated the role of NO by blocking its synthesis with N(G)-nitro-arginine methyl ester (L-NAME) and assessed ex vivo vascular reactivity to acetylcholine.

    • Main Results:

    • M40403 significantly decreased MAP in SHR but not in WKY rats.
    • Blocking NO synthesis with L-NAME abolished the anti-hypertensive effect of M40403.
    • M40403 treatment improved endothelial dysfunction in SHR and reduced nitrotyrosine staining, indicating decreased peroxynitrite formation.

    Conclusions:

    • Overt superoxide production in SHR rats inactivates nitric oxide (NO), leading to reduced blood vessel tone and hypertension.
    • Superoxide-mediated endothelial dysfunction contributes to hypertension.
    • Selective removal of superoxide by M40403 restores blood pressure to near-normal levels and improves vascular function.