The general hypothesis to be tested is that the response of the maternal placental vascular bed to vasodilators depends on, a) the preexisting state of the vascular bed, b) the dose of the vasodilator which is given and c) the gestational age at which the vasodilator is given. Corollaries to this hypothesis are that the action of the vasodilators of the maternal placental vascular bed can best be described when that bed has been previously constricted and has a vasodilatory reserve; that the maternal placental vascular response to PGI2 is biphasic; that the anomalous response to PGI2 is a property of the vascular bed rather than the specific substance used and that the response of the maternal placental vascular bed is not constant but dependent upon gestational age. Experiments will be done with chronically catheterized sheep using a retrograde uterine arterial catheter and flowprobe such that the concentration of vasodilator in blood serving a region of the uterus and placenta can be fixed. Dose response curves will be obtained in response to adenosine and PGI2 infusion. These will be performed at several different gestational ages to observe the effect of gestational age. The effect of insulin on response to adenosine will also be examined. The hypothesis that the maternal placental vascular bed is difficult to dilate because it has no vasodilatory reserve will be tested by inducing a vasodilatory reserve using angiotensin II as a constrictor and repeating the above experiments. We hypothesize that the dose response curve to PGI2 and adenosine will be biphasic with dilatation occurring at the low concentrations and constriction at the high concentrations. These responses may intensify as the placenta ages. We predict that the overlying nonplacental uterine tissue will show normal vasodilating responses at all doses studies.
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