In vivo modulation of norepinephrine-induced cerebral oxygenation states by hypoxia and hyperoxia.
The effect of intravenous norepinephrine (NE) administration on three O2-dependent parameters of cerebral oxygenation was studied in the parietal cortex of skull intact anesthetized rats. Reflectance spectrophotometry was used to measure in vivo changes in cortical hemoglobin saturation (Hb/HbO2), blood volume (BV), and cytochrome c oxidase (cyt. a,a3) oxidation-reduction state. The influence of arterial pressure of oxygen (paO2) on norepinephrine-induced changes in cortical microcirculatory O2 delivery and cyt. a,a3 redox state was tested under conditions of normoxia, hypoxia, and hyperoxia. Norepinephrine produced cyt. a,a3 redox changes which were independent of compensatory alterations in cortical blood volume and changes in systemic blood pressure at the tested physiological extremes. During normoxia, NE caused dose-dependent systemic pressure-related increases in the oxidation level of cyt. a,a3. Conversely, in hypoxia NE caused a reduction. Microcirculatory and cyt. a,a3 redox responses to low doses of NE during hyperoxia were similar to those obtained at high doses during normoxia. The kinetic pattern of changes in hemoglobin saturation, cyt. a,a3 redox state, and cortical blood volume during normoxia and hypoxia was consistent with direct alteration in oxygen delivery to the respiratory chain and possible modification of cerebral oxidative metabolism. Blood-brain barrier alterations and vascular smooth muscle resistance changes to NE under tested conditions of oxygenation are postulated to be responsible for the observed results.
Sylvia
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Piantadosi
C A
CA
D000818:Animals; D003576:Electron Transport Complex IV / Q000378:metabolism; D008297:Male; D008833:Microcirculation / Q000187:drug effects; D008928:Mitochondria / Q000378:metabolism; D009638:Norepinephrine / Q000494:pharmacology*; D010084:Oxidation-Reduction / Q000187:drug effects; D010100:Oxygen / Q000097:blood*; D010108:Oxyhemoglobins / Q000032:analysis; D010296:Parietal Lobe / Q000032:analysis / Q000098:blood supply / Q000187:drug effects*; D051381:Rats; D011919:Rats, Inbred Strains
D010108:Oxyhemoglobins; D003576:Electron Transport Complex IV; D010100:Oxygen; D009638:Norepinephrine