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

Abstract

Reactive oxygen species (ROS) are implicated in vascular homeostasis. This study investigated whether O2.-, the foundation molecule of all ROS, regulates vasomotor function. Hence, vascular reactivity was measured using rat thoracic aortas exposed to an O2.- generator (pyrogallol) which dose-dependently regulated both α-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 μM) and higher (10 - 100 μM) 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 H2O2 that may be produced during experiments did not alter vascular functions. These findings suggest that the nature of O2.--evoked vascular function is determined by its local concentration and the presence of a functional endothelium.