Reactive oxygen species in the cerebral circulation: are they all bad?
Reactive oxygen species (ROS) are a diverse family of molecules generated by all cells. ROS may serve as important cell-signalling molecules in the cerebral circulation. Indeed, in contrast to systemic arteries, major products of superoxide metabolism, including hydrogen peroxide, are powerful cerebral vasodilators, raising the possibility that ROS represent important molecules for increasing local cerebral blood flow. Two major determinants of the overall effects of ROS on cerebrovascular tone are the rate of production of the parent molecule, superoxide, and its rate of metabolism by superoxide dismutases. Although the major enzymatic source of ROS in cerebral arteries has not been clarified, nicotinamide adenine dinucleotide phosphate, reduced form (NADPH)-oxidases, along with cyclooxygenases and lipoxygenases, are probably the primary sources. In cerebral arteries, activation of NADPH-oxidase elicits both an increase in superoxide production and vasodilatation. The identity of the ROS molecule responsible for the vasodilator effects may be hydrogen peroxide, generated from the dismutation of superoxide. NADPH-oxidase activity and function appears to be profoundly greater in cerebral versus systemic arteries. Furthermore, NADPH-oxidase-derived ROS partly contribute to flow-dependent dilatation and may offset angiotensin II-induced constriction of cerebral arteries, consistent with the hypothesis that NADPH-oxidase-derived ROS may play a physiologic role in the control of cerebrovascular tone.
Miller
Alyson A
AA
Department of Pharmacology, The University of Melbourne, Parkville, Victoria, Australia.
Drummond
Grant R
GR
Sobey
Christopher G
CG
D000818:Animals; D001488:Basilar Artery / Q000187:drug effects / Q000378:metabolism; D002560:Cerebrovascular Circulation / Q000187:drug effects* / Q000502:physiology*; D005544:Forecasting; D006861:Hydrogen Peroxide / Q000494:pharmacology; D008084:Lipoxygenase / Q000378:metabolism; D008954:Models, Biological; D019255:NADPH Oxidases / Q000378:metabolism; D011451:Prostaglandin-Endoperoxide Synthases / Q000378:metabolism; D051381:Rats; D017382:Reactive Oxygen Species / Q000378:metabolism* / Q000494:pharmacology*; D012039:Regional Blood Flow; D015398:Signal Transduction / Q000502:physiology; D013482:Superoxide Dismutase / Q000378:metabolism; D013481:Superoxides / Q000378:metabolism; D014664:Vasodilation / Q000187:drug effects / Q000502:physiology; D014665:Vasodilator Agents / Q000494:pharmacology
D017382:Reactive Oxygen Species; D014665:Vasodilator Agents; D013481:Superoxides; D006861:Hydrogen Peroxide; D008084:Lipoxygenase; D011451:Prostaglandin-Endoperoxide Synthases; D013482:Superoxide Dismutase; D019255:NADPH Oxidases