This proposal is designed to determine the specific hemodynamic response of human uterine arteries through the menstrual cycle and in to early gestation. A series of longitudinal observations wil be made in each of 25 subjects. These observations will begin in the early follicular phase and continue through early pregnancy. We will measure uterine artery impedance and blood flow employing Doppler techniques. In addition, we intend to measure changes in intravascular volume over this same time course utilizing Evans blue dye dilution. This will allow indexing of the changes in uterine artery blood flow to overflow changes in intravascular volume. These measurements will be correlated to maternal angiotensinogen genotype, as well as maternal serum estrogen, progesterone, reni, and aldosterone at six different points including follicular, preovulatory, mid luteal, early pregnancy and six and twilve weeks of amenorrhea.
The specific aims are: 1) to determine whether the changes in uterine artery blood flow are associated with parallel changes in intravascular volume or whether uterine artery hemodynamic response represents an independent adaptation unique to the local environment, 2) to demonstrate that either a specific hormonal milieu, or a genetic predisposition (as reflected by angiotensinogen genotype) determines uterine artery blood flow, impedance and total intravascular volume, 3) to demonstrate that the maternal uterine artery hemodynamic and intravascular volume changes occurring during the luteal phase of the menstrual cycle and in early pregnancy are representative of an inherent maternal responsiveness to hormonal signaling. As a result, physiologic changes apparent in individuals during the menstrual cycle will be paralleled by the early maternal adaptation to pregnancy. Over the course of the menstrual cycle and in early pregnancy we intend to 1) characterize both impedance and blood flow within the uterine and radial (control) arteries, 2) determine changes in intravascular volume, 3) define the hormonal environment associated with specific changes in intravascular volume and uterine artery hemodynamics.
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