Hemodilutional anemia is associated with increased cerebral neuronal nitric oxide synthase gene expression.
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 (Pbr(O(2))) decreased transiently from 17.3 +/- 4.1 to 14.4 +/- 4.1 Torr (P < 0.05), before returning to baseline after approximately 20 min. An increase in CBF may have contributed to restoring Pbr(O(2)) 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-1beta were observed after anemia or hypoxia. Hemodilutional anemia caused an acute reduction in Pbr(O(2)) and an increase in cerebral cortical nNOS mRNA, supporting a role for nNOS in the physiological response to acute anemia.
Hare
Gregory M T
GM
Department of Anaesthesia, University of Toronto, St. Michael's Hospital, Toronto M5B 1W8, Canada. hareb@smh.toronto.on.ca
Mazer
C David
CD
Mak
William
W
Gorczynski
Reginald M
RM
Hum
Kathryn M
KM
Kim
Steve Y
SY
Wyard
Leslie
L
Barr
Aiala
A
Qu
Rong
R
Baker
Andrew J
AJ
D000740:Anemia / Q000201:enzymology* / Q000209:etiology*; D000818:Animals; D001784:Blood Gas Analysis; D001923:Brain Chemistry / Q000235:genetics*; D002138:Calibration; D002560:Cerebrovascular Circulation / Q000502:physiology; D004587:Electrophoresis, Agar Gel; D015971:Gene Expression Regulation, Enzymologic / Q000235:genetics*; D006438:Hemodilution / Q000009:adverse effects*; D006454:Hemoglobins / Q000378:metabolism; D000860:Hypoxia / Q000201:enzymology; D017078:Laser-Doppler Flowmetry; D008839:Microelectrodes; D019001:Nitric Oxide Synthase / Q000096:biosynthesis* / Q000235:genetics; D052248:Nitric Oxide Synthase Type I; D052250:Nitric Oxide Synthase Type III; D011048:Polarography; D012333:RNA, Messenger / Q000096:biosynthesis; D051381:Rats; D017207:Rats, Sprague-Dawley; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015854:Up-Regulation
D006454:Hemoglobins; D012333:RNA, Messenger; D019001:Nitric Oxide Synthase; D052248:Nitric Oxide Synthase Type I; D052250:Nitric Oxide Synthase Type III; C496322:Nos1 protein, rat; C496316:Nos3 protein, rat