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(Circulation Research. 2002;91:1031.)
© 2002 American Heart Association, Inc.

Integrative Physiology

Regulation of the Brain’s Vascular Responses to Oxygen

Ivan T. Demchenko, Tim D. Oury, James D. Crapo, Claude A. Piantadosi

From Duke University Medical Center (I.T.D., C.A.P.), Durham NC; the University of Pittsburgh Medical Center (T.D.O.), Pittsburgh, Pa; and the National Jewish Medical Center (J.D.C.), Denver, Colo.

Correspondence to Dr Claude A. Piantadosi, Box 3315, Duke University Medical Center, Durham, NC 27710. E-mail piant001{at}mc.duke.edu

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^·.

Key Words: cerebral blood flow • hyperoxia • superoxide dismutase • nitric oxide • peroxynitrite

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