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.

R01HL060131

1999-01-01

2004-12-31