The most consistent and vigorous fetal cardiovascular response occurs in the defense of fetal (rental) arterial blood pressure, as elicited, for instance, by supra-renal stenosis of the fetal aorta. Part of this response is the activation of the fetal renin angiotensin system. When angiotensin is chronically infused into normal fetuses, at very low dose rates, there is a slowly developing but very large increase in fetal arterial blood pressure. But there is also a great increase in placental water transfer into the fetus, as evidenced by polyhydramnios in intact fetuses and hydrops fetalis in nephrectomized fetuses. It is hypothesized, therefor, that the modulation of placental water transfer from the mother into the conceptus is part of the homeostatic mechanism that controls fetal arterial pressure and that polyhydramnios and hydrops are derailments of that homeostatic mechanism.
Specific aims of the proposed experiments are, first, to unravel the physiological regulation mechanism that acts within the placenta to control water transfer and, second, to quantify the relevant hemodynamic and membrane parameters. Fetal sheep with indwelling catheters and electronic instrumentation will be used. Placental flows and pressures will be measured in the presence of partial venous obstruction with and without the concomitant administration of angiotensin. The long-term goal of our research program is to help clarify the pathophysiology of human polyhydramnios, a common disease of pregnancy, and of hydrops fetalis, an uncommon but usually fatal disease of the newborn.
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