The bimodal regulation of vascular function by superoxide anion: role of endothelium.
Reactive oxygen species (ROS) are implicated in vascular homeostasis. This study investigated whether O(2) (*-), the foundationmolecule of all ROS, regulates vasomotor function. Hence, vascular reactivity was measured using rat thoracic aortas exposed to an O(2) (*-) 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 microM) and higher (10 - 100 microM) 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(2)O(2) that may be produced during experiments did not alter vascular functions. These findings suggest that the nature of O(2) (*-)-evoked vascular function is determined by its local concentration and the presence of a functional endothelium.
Demirci
Buket
B
Department of Medicine and Therapeutics, Institute of Clinical Science, Queen's University Belfast, Belfast, UK.
McKeown
Pascal P
PP
Dvm
Ulvi Bayraktutan
UB
D000818:Animals; D001011:Aorta / Q000187:drug effects* / Q000378:metabolism*; D002374:Catalase / Q000378:metabolism; D004121:Dimethyl Sulfoxide / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004727:Endothelium / Q000187:drug effects* / Q000378:metabolism*; D016166:Free Radical Scavengers / Q000494:pharmacology; D066298:In Vitro Techniques; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects; D010656:Phenylephrine / Q000494:pharmacology; D011166:Porphyrins / Q000494:pharmacology; D011748:Pyrogallol / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D013481:Superoxides / Q000494:pharmacology*; D014664:Vasodilation / Q000187:drug effects
D016166:Free Radical Scavengers; D011166:Porphyrins; D011748:Pyrogallol; D013481:Superoxides; D010656:Phenylephrine; C021096:tetra(4-N-methylpyridyl)porphine; D002374:Catalase; D004121:Dimethyl Sulfoxide