The investigator proposes to determine the mechanisms by which pregnancy and chronic hypoxia influence uterine artery vasoregulation and growth, and thus contribute to fetal growth restriction and possibly pre-eclampsia. The central working hypothesis is that chronic hypoxia impairs vasoregulatory and growth related responses of the uterine artery. The hypothesis will be tested by experiments performed in three specific aims. (1) Determine the effects of pregnancy and chronic hypoxia on uterine artery vasodilators/constrictor responses to the physiological stimuli of flow, pressure, and pharmacological agents; (2) Determine the effect of pregnancy and/or chronic hypoxia on uterine artery growth; and (3) Determine the effect of pregnancy and/or chronic hypoxia on the relationship of indices of impaired uterine artery vasoregulation and growth to uterine artery blood flow, intrauterine growth restriction, and pre-eclampsia.
Aims #1 and #2 are to be conducted on pregnant and non-pregnant guinea pigs kept at 1600m and 3962m throughout pregnancy.
Aim #3 focuses on women residing at either low or high altitude in whom Doppler flow velocimetry and ultrasound imaging will be used to measure uterine artery blood flow.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Project (R01)
Project #
5R01HL060131-02
Application #
6139286
Study Section
Human Embryology and Development Subcommittee 1 (HED)
Project Start
1999-01-01
Project End
2003-12-31
Budget Start
2000-01-01
Budget End
2000-12-31
Support Year
2
Fiscal Year
2000
Total Cost
$305,923
Indirect Cost
Name
University of Colorado Denver
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
065391526
City
Aurora
State
CO
Country
United States
Zip Code
80045
Schwartz, Joel; Cioffi-Ragan, Darleen; Wilson, Megan J et al. (2013) Little effect of gestation at 3,100 m on fetal fat accretion or the fetal circulation. Am J Hum Biol 25:544-9
Dávila, R Daniela; Julian, Colleen G; Browne, Vaughn A et al. (2012) Role of cytokines in altitude-associated preeclampsia. Pregnancy Hypertens 2:65-70
Julian, Colleen G; Hageman, Jennifer L; Wilson, Megan J et al. (2011) Lowland origin women raised at high altitude are not protected against lower uteroplacental O2 delivery during pregnancy or reduced birth weight. Am J Hum Biol 23:509-16
Dávila, R Daniela; Julian, Colleen G; Wilson, Megan J et al. (2011) Do cytokines contribute to the Andean-associated protection from reduced fetal growth at high altitude? Reprod Sci 18:79-87
Moore, Lorna G; Charles, Shelton M; Julian, Colleen G (2011) Humans at high altitude: hypoxia and fetal growth. Respir Physiol Neurobiol 178:181-90
Dávila, R Daniela; Julian, Colleen G; Wilson, Megan J et al. (2010) Do anti-angiogenic or angiogenic factors contribute to the protection of birth weight at high altitude afforded by Andean ancestry? Reprod Sci 17:861-70
Bigham, Abigail; Bauchet, Marc; Pinto, Dalila et al. (2010) Identifying signatures of natural selection in Tibetan and Andean populations using dense genome scan data. PLoS Genet 6:e1001116
Bennett, Adam; Sain, Stephen R; Vargas, Enrique et al. (2008) Evidence that parent-of-origin affects birth-weight reductions at high altitude. Am J Hum Biol 20:592-7
Julian, Colleen Glyde; Galan, Henry L; Wilson, Megan J et al. (2008) Lower uterine artery blood flow and higher endothelin relative to nitric oxide metabolite levels are associated with reductions in birth weight at high altitude. Am J Physiol Regul Integr Comp Physiol 295:R906-15
Moore, Lorna G; Niermeyer, Susan; Vargas, Enrique (2007) Does chronic mountain sickness (CMS) have perinatal origins? Respir Physiol Neurobiol 158:180-9

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