Involvement of extracellular superoxide dismutase in regulating brain blood flow.
The physiological role of extracellular superoxide dismutase (SOD3) has received insufficient study. We investigated the hypothesis that SOD3, which neutralizes superoxide anions (O2(-)) in the intercellular space of the brain, prevents the inactivation of nitric oxide (NO) and is thus involved in regulating cerebral vascular tone. Local brain blood flow was measured in the striatum of anesthetized rats during administration of various combinations of a SOD mimetic, a SOD inhibitor, an NO donor, and an NOS inhibitor into the striatum using a Hamilton syringe. In normal conditions, SOD3 was found to minimize O2(-) levels, protecting endogenously produced NO at a sufficient level to maintain cerebral vascular tone and reactivity. SOD3 was found to increase the vasodilatory effect of endogenously produced NO in the brain. SOD3 was found to neutralize superoxide anions produced in the brain during respiration of 100% O2 and to maintain basal NO levels and its vasodilatory potential in normobaric hyperoxia.
Demchenko
I T
IT
I. M. Sechenov Institute of Evolutionary Physiology and Biochemistry, 44 M. Torez Prospekt, 194223 St. Petersburg, Russia. jil@iephb.ru
Gutsaeva
D R
DR
Moskvin
A N
AN
Zhilyaev
S Yu
SY
D000818:Animals; D001808:Blood Vessels / Q000187:drug effects / Q000201:enzymology / Q000502:physiology; D001921:Brain / Q000098:blood supply* / Q000187:drug effects / Q000502:physiology*; D002560:Cerebrovascular Circulation / Q000187:drug effects / Q000502:physiology*; D003342:Corpus Striatum / Q000098:blood supply / Q000187:drug effects / Q000502:physiology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005110:Extracellular Space / Q000187:drug effects / Q000502:physiology; D018496:Hyperoxia / Q000378:metabolism; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009569:Nitric Oxide / Q000378:metabolism; D020030:Nitric Oxide Donors / Q000494:pharmacology; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors / Q000378:metabolism; D051381:Rats; D026423:S-Nitroso-N-Acetylpenicillamine / Q000494:pharmacology; D013482:Superoxide Dismutase / Q000037:antagonists & inhibitors / Q000378:metabolism*; D013481:Superoxides / Q000378:metabolism; D014664:Vasodilation / Q000187:drug effects / Q000502:physiology
D004791:Enzyme Inhibitors; D020030:Nitric Oxide Donors; D013481:Superoxides; D009569:Nitric Oxide; D026423:S-Nitroso-N-Acetylpenicillamine; D019001:Nitric Oxide Synthase; C499089:Sod3 protein, rat; D013482:Superoxide Dismutase; D019331:NG-Nitroarginine Methyl Ester