Endothelium-dependent contractions to oxygen-derived free radicals in the canine basilar artery

Z. S. Katusic, J. Schugel, F. Cosentino, P. M. Vanhoutte

Research output: Contribution to journalArticlepeer-review

110 Scopus citations


Experiments were designed to determine the effect of oxygen-derived free radicals in isolated canine basilar arteries. Rings with and without endothelium were suspended for isometric tension recording in modified Krebs- Ringer bicarbonate solution bubbled with 95% O2-5% CO2 (temperature = 37°C: pH = 7.4). A radioimmunoassay technique was used to measure production of prostaglandins and thromboxane B2. Xanthine oxidase (1-9 mU/ml, in the presence of 10-4 M xanthine) and hydrogen peroxide (10-6 to 10-4 M) caused concentration-dependent contractions. The removal of endothelium reversed these contractions into relaxations. Contractions to xanthine oxidase and hydrogen peroxide were inhibited in the presence of superoxide dismutase (150 U/ml), catalase (1,200 U/ml), indomethacin (10-5 M), and SQ 29548 (10-6 M) but not in the presence of deferoxamine (10-4 to 10-3 M) and dimethyl sulfoxide (10-4 M). N(G)-monomethyl-L-arginine (3 x 10-5 M) augmented the contractions to hydrogen peroxide. Xanthine oxidase stimulated production of 6-keto-prostaglandin F(1α), prostaglandin F(2α), prostaglandin E2, and thromboxane B2. The stimulatory effect was prevented by the removal of endothelial cells. These studies suggest that xanthine oxidase causes endothelium-dependent contractions mediated by 1) hydrogen peroxide-induced stimulation of the endothelial metabolism of arachidonic acid via the cyclooxygenase pathway, leading to activation of prostaglandin H2-thromboxane A2 receptors, and 2) inactivation of basal production of nitric oxide by superoxide anions.

Original languageEnglish (US)
Pages (from-to)H859-H864
JournalAmerican Journal of Physiology - Heart and Circulatory Physiology
Issue number3 33-3
StatePublished - 1993


  • cyclooxygenase
  • hydrogen peroxide
  • prostaglandin H-thromboxane A receptors
  • superoxide anion

ASJC Scopus subject areas

  • Physiology
  • Cardiology and Cardiovascular Medicine
  • Physiology (medical)


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