AJP - Regu AJP: Cell Physiology
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
QUICK SEARCH:   [advanced]


     

Am J Physiol Regul Integr Comp Physiol 292: R403-R414, 2007. First published September 14, 2006; doi:10.1152/ajpregu.00403.2006
0363-6119/07 $8.00
This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow All Versions of this Article:
292/1/R403    most recent
00403.2006v1
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in Web of Science
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Web of Science (11)
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by McLaren, A. T.
Right arrow Articles by Hare, G. M. T.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by McLaren, A. T.
Right arrow Articles by Hare, G. M. T.

NEUROHUMORAL CONTROL OF CARDIOVASCULAR FUNCTION

Increased expression of HIF-1{alpha}, nNOS, and VEGF in the cerebral cortex of anemic rats

Anya T. McLaren,1,2 Philip A. Marsden,3 C. David Mazer,1,2 Andrew J. Baker,1 Duncan J. Stewart,4 Albert K. Y. Tsui,1,2 Xiaomao Li,1,5 Yeni Yucel,6,7 Malcolm Robb,4 Shelley R. Boyd,7 Elaine Liu,1 Julie Yu,1 and Gregory M. T. Hare1,2

1Department of Anesthesia, Cara Phelan Trauma Research Centre, 3Division of Nephrology, 4Division of Cardiology, 6Department of Laboratory Medicine and Pathobiology, 7Department of Opthalmology, University of Toronto, St. Michael's Hospital, Toronto, Ontario; 2Department of Physiology, University of Toronto, Toronto, Ontario; and 5Biotechnology Centre for Applied Research and Training, Seneca College, Toronto, Ontario, Canada

Submitted 8 June 2006 ; accepted in final form 30 August 2006

This study tested the hypothesis that specific hypoxic molecules, including hypoxia-inducible factor-1{alpha} (HIF-1{alpha}), neuronal nitric oxide synthase (nNOS), and vascular endothelial growth factor (VEGF), are upregulated within the cerebral cortex of acutely anemic rats. Isoflurane-anesthetized rats underwent acute hemodilution by exchanging 50% of their blood volume with pentastarch. Following hemodilution, mean arterial pressure and arterial PaO2 values did not differ between control and anemic rats while the hemoglobin concentration decreased to 57 ± 2 g/l. In anemic rats, cerebral cortical HIF-1{alpha} protein levels were increased, relative to controls (1.7 ± 0.5-fold, P < 0.05). This increase was associated with an increase in mRNA levels for VEGF, erythropoietin, CXCR4, iNOS, and nNOS (P < 0.05 for all), but not endothelial NOS. Cerebral cortical nNOS and VEGF protein levels were increased in anemic rats, relative to controls (2.0 ± 0.2- and 1.5 ± 0.4-fold, respectively, P < 0.05 for both). Immunohistochemistry demonstrated increased HIF-1{alpha} and VEGF staining in perivascular regions of the anemic cerebral cortex and an increase in the number of nNOS-positive cerebral cortical cells (3.2 ± 1.0-fold, P < 0.001). The nNOS-positive cells costained with the neuronal marker, Neu-N, but not with the astrocytic marker glial fibrillary acidic protein (GFAP). These nNOS-positive neurons frequently sent axonal projections toward cerebral blood vessels. Conversely, VEGF immunostaining colocalized with both neuronal (NeuN) and astrocytic markers (GFAP). In conclusion, acute normotensive, normoxemic hemodilution increased the levels of HIF-1{alpha} protein and mRNA for HIF-1-responsive molecules. nNOS and VEGF protein levels were also increased within the cerebral cortex of anemic rats at clinically relevant hemoglobin concentrations.

hemodilution; cerebral hypoxia


Address for reprint requests and other correspondence: G. M. T. Hare, Dept. of Anesthesia and Physiology, Univ. of Toronto, St. Michael's Hospital, 30 Bond St., Toronto, Ontario, M5B 1W8, Canada (e-mail: hareg{at}smh.toronto.on.ca)




This article has been cited by other articles:


Home page
 StrokeHome page
M. Oddo, A. Milby, I. Chen, S. Frangos, E. MacMurtrie, E. Maloney-Wilensky, M. Stiefel, W. A. Kofke, J. M. Levine, and P. D. Le Roux
Hemoglobin Concentration and Cerebral Metabolism in Patients With Aneurysmal Subarachnoid Hemorrhage
Stroke, April 1, 2009; 40(4): 1275 - 1281.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Physiol. Regul. Integr. Comp. Physiol.Home page
R. El Hasnaoui-Saadani, A. Pichon, D. Marchant, P. Olivier, T. Launay, P. Quidu, M. Beaudry, A. Duvallet, J.-P. Richalet, and F. Favret
Cerebral adaptations to chronic anemia in a model of erythropoietin-deficient mice exposed to hypoxia
Am J Physiol Regulatory Integrative Comp Physiol, March 1, 2009; 296(3): R801 - R811.
[Abstract] [Full Text] [PDF]

Home page
 Circ. Res.Home page
D. L. Diesen, D. T. Hess, and J. S. Stamler
Hypoxic Vasodilation by Red Blood Cells: Evidence for an S-Nitrosothiol-Based Signal
Circ. Res., August 29, 2008; 103(5): 545 - 553.
[Abstract] [Full Text] [PDF]

Home page
 J. Appl. Physiol.Home page
G. M. T. Hare, C. D. Mazer, J. S. Hutchison, A. T. McLaren, E. Liu, A. Rassouli, J. Ai, R. E. Shaye, J. A. Lockwood, C. E. Hawkins, et al.
Severe hemodilutional anemia increases cerebral tissue injury following acute neurotrauma
J Appl Physiol, September 1, 2007; 103(3): 1021 - 1029.
[Abstract] [Full Text] [PDF]


HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
Visit Other APS Journals Online
Copyright © 2007 by the American Physiological Society.