Blockade of platelet-mediated relaxation in rat aortic rings exposed to xanthine-xanthine oxidase

B. C. Yang, S. Khan, J. L. Mehta

Research output: Contribution to journalArticlepeer-review

Abstract

Platelet-induced relaxation of endothelium-intact vascular tissues, mediated via release of endothelium-derived relaxing factor (EDRF), is diminished or lost after ischemia and reperfusion. Release of oxygen free radicals during ischemia-reperfusion may degrade EDRF and influence response of vascular tissues to platelets. To determine platelet modulation of tone of blood vessels treated with oxygen free radicals, rat aortic rings with intact endothelium were exposed to xanthine (X) plus xanthine oxidase (XO) 5 min before contraction with norepinephrine followed by exposure of rings to platelets. Treatment of aortic rings with X + XO caused a modest contraction, potentiated norepinephrine-mediated contraction, and inhibited platelet- mediated vasorelaxation. Exposure of aortic rings to X + XO also decreased ADP- as well as acetylcholine-mediated relaxation. Pretreatment of rings with superoxide dismutase or catalase did not change X + XO-induced inhibition of platelet-mediated relaxation, but it abolished the X + XO-induced contraction of rings as well as subsequent potentiation of norepinephrine-mediated contraction. Pretreatment of rings with hydroxyl radical scavengers dimethyl- 2-thiourea, dimethyl sulfoxide, mannitol, or histidine attenuated the X + XO- induced inhibition of platelet-mediated relaxation, although these agents did not affect X + XO-induced contraction of rings. This study indicates that the vasoconstriction on exposure of aortic rings to X + XO is due to generation of superoxide anions, whereas inhibition of platelet-mediated relaxation after exposure of vessels to X + XO is due, at least in part, to release of hydroxyl radicals. Release of superoxide anions and hydroxyl radicals after temporary arterial occlusion may be the basis of subsequent modulation of vascular tone.

Original languageEnglish (US)
JournalAmerican Journal of Physiology - Heart and Circulatory Physiology
Volume266
Issue number6 35-6
StatePublished - 1994
Externally publishedYes

Keywords

  • endothelium-derived relaxing factor
  • oxygen-derived free radicals
  • vasorelaxation

ASJC Scopus subject areas

  • Physiology

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