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The bimodal regulation of vascular function by superoxide anion: role of endothelium

  • Demirci, Buket (Department of Medicine and Therapeutics, Institute of Clinical Science, Queen's University Belfast) ;
  • McKeown, Pascal P. (Department of Medicine and Therapeutics, Institute of Clinical Science, Queen's University Belfast) ;
  • Bayraktutan DVM, Ulvi (Division of Stroke Medicine, Clinical Sciences Building, University of Nottingham)
  • Received : 2007.06.04
  • Accepted : 2007.09.10
  • Published : 2008.03.31

Abstract

Reactive oxygen species (ROS) are implicated in vascular homeostasis. This study investigated whether ${O_2}^{\cdot^-}$, the foundation molecule of all ROS, regulates vasomotor function. Hence, vascular reactivity was measured using rat thoracic aortas exposed to an ${O_2}^{\cdot^-}$ generator (pyrogallol) which dose-dependently regulated both $\alpha$-adrenergic agonist-mediated contractility to phenylephrine and endothelium-dependent relaxations to acetylcholine. Pyrogallol improved and attenuated responses to acetylcholine at its lower (10 nM - 1 ${\mu}M$) and higher (10 - 100 ${\mu}M$) concentrations, respectively while producing the inverse effects with phenylephrine. The endothelial inactivation by L-NAME abolished acetylcholine-induced vasodilatations but increased phenylephrine and KCl-induced vasoconstrictions regardless of the pyrogallol dose used. Relaxant responses to sodium nitroprusside, a nitric oxide donor, were not affected by pyrogallol. Other ROS i.e. peroxynitrite and $H_2O_2$ that may be produced during experiments did not alter vascular functions. These findings suggest that the nature of ${O_2}^{\cdot^-}$-evoked vascular function is determined by its local concentration and the presence of a functional endothelium.

Keywords

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