Regulation of the brain's vascular responses to oxygen.

Published

Journal Article

The mechanism of oxygen-induced cerebral vasoconstriction has been sought for more than a century. Using genetically altered mice to enhance or disrupt extracellular superoxide dismutase (EC-SOD, SOD3), we tested the hypothesis that this enzyme plays a critical role in the physiological response to oxygen in the brain by regulating nitric oxide (NO*) availability. Cerebral blood flow responses in these genetically altered mice to changes in PO2 demonstrate that SOD3 regulates equilibrium between superoxide (*O2-) and NO*, thereby controlling vascular tone and reactivity in the brain. That SOD3 opposes inactivation of NO* is shown by absence of vasoconstriction in response to PO2 in the hyperbaric range in SOD3+/+ mice, whereas NO-dependent relaxation is attenuated in SOD3-/- mutants. Thus, EC-SOD promotes NO* vasodilation by scavenging *O2- while hyperoxia opposes NO* and promotes constriction by enhancing endogenous *O2- generation and decreasing basal vasodilator effects of NO*.

Full Text

Duke Authors

Cited Authors

  • Demchenko, IT; Oury, TD; Crapo, JD; Piantadosi, CA

Published Date

  • November 29, 2002

Published In

Volume / Issue

  • 91 / 11

Start / End Page

  • 1031 - 1037

PubMed ID

  • 12456489

Pubmed Central ID

  • 12456489

Electronic International Standard Serial Number (EISSN)

  • 1524-4571

Language

  • eng

Conference Location

  • United States