Hemodilutional anemia is associated with increased cerebral neuronal nitric oxide synthase gene expression

Abstract

Severe hemodilutional anemia may reduce cerebral oxygen delivery, resulting in cerebral tissue hypoxia. Increased nitric oxide synthase (NOS) expression has been identified following cerebral hypoxia and may contribute to the compensatory increase in cerebral blood flow (CBF) observed after hypoxia and anemia. However, changes in cerebral NOS gene expression have not been reported after acute anemia. This study tests the hypothesis that acute hemodilutional anemia causes cerebral tissue hypoxia, triggering changes in cerebral NOS gene expression. Anesthetized rats underwent hemodilution when 30 ml/kg of blood were exchanged with pentastarch, resulting in a final hemoglobin concentration of 51.0 ± 1.2 g/l ( n = 7 rats). Caudate tissue oxygen tension (PbrO2 ) decreased transiently from 17.3 ± 4.1 to 14.4 ± 4.1 Torr ( P < 0.05), before returning to baseline after ∼20 min. An increase in CBF may have contributed to restoring PbrO2 by improving cerebral tissue oxygen delivery. An increase in neuronal NOS (nNOS) mRNA was detected by RT-PCR in the cerebral cortex of anemic rats after 3 h ( P < 0.05, n = 5). A similar response was observed after exposure to hypoxia. By contrast, no increases in mRNA for endothelial NOS or interleukin-1β were observed after anemia or hypoxia. Hemodilutional anemia caused an acute reduction in PbrO2 and an increase in cerebral cortical nNOS mRNA, supporting a role for nNOS in the physiological response to acute anemia.