Abstract
The mammalian fetus is highly adapted for growth in a low-O2 environment in which arterial O2 tensions average near 30 mm Hg. Acute decreases in O2 tension below this value elicit vasodilatation, but the responses are blunted compared to those observed in adults. Chronic hypoxia in the fetus stimulates a pattern of cerebrovascular remodeling that results in an increased wall thickness and decreased overall contractility and also depresses the capacity for cerebral vasodilatation through decreases in NO release, soluble guanylate cyclase activity, and expression of PKG substrates. Many of these hypoxic effects appear to be homeostatic and may be mediated by VEGFs, which increase in direct response to hypoxia and, in turn, can dramatically alter the expression and function of multiple contractile proteins in cerebrovascular smooth muscle through both endothelium-dependent and endothelium-independent effects on large artery smooth muscle.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
Preview
Unable to display preview. Download preview PDF.
References
Eastman NJ (1954) Mount everest in utero. Am J Obstet Gynecol 67:701-11.
Bank A (2006) Regulation of human fetal hemoglobin: new players, new complexities. Blood 107:435-43.
Blood AB, Hunter CJ, Power GG (2003) Adenosine mediates decreased cerebral metabolic rate and increased cerebral blood flow during acute moderate hypoxia in the near-term fetal sheep. J Physiol 553:935-45.
Nishida N, Blood AB, Hunter CJ, Bragg S, Williams J, Pearce WJ, Power GG (2006) Role of prostanoids in the regulation of cerebral blood flow during normoxia and hypoxia in the fetal sheep. Pediatr Res 60:524-9.
Pearce WJ, Ashwal S (1987) Developmental changes in thickness, contractility, and hypoxic sensitivity of newborn lamb cerebral arteries. Pediatr Res 22:192-6.
Pearce WJ, Ashwal S, Cuevas J (1989) Direct effects of graded hypoxia on intact and denuded rabbit cranial arteries. Am J Physiol 257:H824-33.
Zurcher SD, Ong-Veloso GL, Akopov SE, Pearce WJ (1998) Maturational modification of hypoxic relaxation in ovine carotid and cerebral arteries: role of endothelium. Biol Neonate 74:222-32.
Salihagic-Kadic A, Medic M, Jugovic D, Kos M, Latin V, Kusan Jukic M, Arbeille P (2006) Fetal cerebrovascular response to chronic hypoxia–implications for the prevention of brain damage. J Matern Fetal Neonatal Med 19:387-96.
Larsen GA, Skjellegrind HK,VinjeML, Berg-Johnsen J (2008)Mitochondria aremore resistant to hypoxic depolarization in the newborn than in the adult brain. Neurochem Res 33:1894-900.
Rees S, Harding R, Walker D (2008) An adverse intrauterine environment: implications for injury and altered development of the brain. Int J Dev Neurosci 26:3-11.
Williams JM, Pearce WJ (2006) Age-dependent modulation of endothelium-dependent vasodilatation by chronic hypoxia in ovine cranial arteries. J Appl Physiol 100:225-32.
Teng GQ, Williams J, Zhang L, Purdy R, Pearce WJ (1998 Sep) Effects of maturation, artery size, and chronic hypoxia on 5-HT receptor type in ovine cranial arteries. Am J Physiol 275:R742-53.
Nauli SM, Williams JM, Gerthoffer WT, Pearce WJ (2005) Chronic hypoxia modulates relations among calcium, myosin light chain phosphorylation, and force differently in fetal and adult ovine basilar arteries. J Appl Physiol 99:120-7.
Pearce WJ,Williams JM,White CR, Lincoln TM(2009) Effects of chronic hypoxia on soluble guanylate cyclase activity in fetal and adult ovine cerebral arteries. J Appl Physiol 107:192-9.
Hoeben A, Landuyt B, Highley MS, Wildiers H, Van Oosterom AT, De Bruijn EA (2004) Vascular endothelial growth factor and angiogenesis. Pharmacol Rev 56:549-80.
Nilsson I, ShibuyaM,Wennstrom S (2004) Differential activation of vascular genes by hypoxia in primary endothelial cells. Exp Cell Res 299:476-85
Storkebaum E, Lambrechts D, Carmeliet P (2004) VEGF: once regarded as a specific angiogenic factor, now implicated in neuroprotection. Bioessays 26:943-54
Marko SB, DamonDH(2008) VEGF promotes vascular sympathetic innervation. AmJ Physiol Heart Circ Physiol 294:H2646-52.
Osada-Oka M, Ikeda T, Imaoka S, Akiba S, Sato T (2008) VEGF-enhanced proliferation under hypoxia by an autocrine mechanism in human vascular smooth muscle cells. J Atheroscler Thromb 15:26-33.
Author information
Authors and Affiliations
Corresponding author
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2011 Springer Science+Business Media, LLC
About this paper
Cite this paper
Pearce, W.J., Butler, S.M., Abrassart, J.M., Williams, J.M. (2011). Fetal Cerebral Oxygenation: The Homeostatic Role of Vascular Adaptations to Hypoxic Stress. In: LaManna, J., Puchowicz, M., Xu, K., Harrison, D., Bruley, D. (eds) Oxygen Transport to Tissue XXXII. Advances in Experimental Medicine and Biology, vol 701. Springer, Boston, MA. https://doi.org/10.1007/978-1-4419-7756-4_30
Download citation
DOI: https://doi.org/10.1007/978-1-4419-7756-4_30
Published:
Publisher Name: Springer, Boston, MA
Print ISBN: 978-1-4419-7755-7
Online ISBN: 978-1-4419-7756-4
eBook Packages: Biomedical and Life SciencesBiomedical and Life Sciences (R0)