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ANEMIA INCEASES RAT CEREBRAL CORTICAL nNOS PROTEIN LEVELS

University of Toronto, St. Michael’s Hospital, 30 Bond Street, Toronto, Ontario M5B 1W8.

INTRODUCTION: Increased cerebral cortical neuronal nitric oxide synthase (nNOS) expression has been identified following exposure to hypoxic environmental conditions (1) and may mediate the associated compensatory increase in cerebral blood flow (CBF) observed during hypoxia (2). As such, nNOS may contribute to neuroprotective mechanisms directed at optimizing CBF during hypoxia. The current study tests the hypothesis that acute hemodilutional anemia causes cerebral hypoxia triggering an increase in cerebral nNOS protein levels at clinically relevant hemoglobin concentrations.

METHODS: With Animal Care Committee approval, anesthetized rats underwent tail artery and vein cannulation to monitor arterial pressure and performing hemodilution. Hemodilutional anemia was achieved by exchanging 30 ml.kg^–1 of blood with pentastarch over 10 minutes. Hemoglobin concentrations were assessed by co-oximetry. Control animals were not hemodiluted. Animals exposed to hypoxia (10% oxygen) served as positive controls. Rats were recovered for 6,12, 24, 48 hours, 4 and 7 days (n=6 rats/group/time). Cerebral cortical nNOS levels were assessed by Western blot analysis. Band density was quantified digitally and reported as pixels µg protein^–1. A two-way ANOVA and post hoc Tukey test were used to assess data. Significance was assigned at p < 0.05 (Mean ± SD).

RESULTS: The hemoglobin concentration in anemic rats decreased to 64 ± 11 g.L^–1 following hemodilution (p<0.05) and then increased toward control values by 7 days. At 12 hours, there was a significant increase in cerebral cortical nNOS protein in both anemic (1,847 ± 195) and hypoxic rats (2,145 ± 138), relative to controls (1121 ± 295) (p<0.05). At 24 hours, nNOS protein remained significantly elevated in hypoxic rats but returned toward control values in anemic rats (1,643 ± 302).

DISCUSSION: Acute hemodilutional anemia caused a transient increase in cerebral cortical nNOS protein, which diminished as the hemoglobin concentration recovered toward control values. Hypoxia produced a more sustained increase in nNOS, supporting the hypothesis that hypoxia may have triggered the increase in nNOS observed in anemic rats. Increased nNOS may contribute to endogenous cerebral neuroprotective mechanisms invoked to protect the brain during anemia. (CAS, PSI Support).

REFERENCES:

1 Adv Exp Med Biol 454:319, 1998.[Medline]

2 J Cereb Blood Flow Metab 20: 220, 2000.[Medline]

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