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.

Agency
National Institute of Health (NIH)
Institute
Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD)
Type
Research Project (R01)
Project #
1R01HD021082-01A1
Application #
3319790
Study Section
Human Embryology and Development Subcommittee 2 (HED)
Project Start
1986-09-01
Project End
1991-08-31
Budget Start
1986-09-01
Budget End
1987-08-31
Support Year
1
Fiscal Year
1986
Total Cost
Indirect Cost
Name
University of Wisconsin Madison
Department
Type
Schools of Medicine
DUNS #
161202122
City
Madison
State
WI
Country
United States
Zip Code
53715
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Reid, D L; Davidson, S R; Phernetton, T M et al. (1992) Influence of terbutaline on ovine uterine response to prostaglandin E2 challenge. Am J Obstet Gynecol 166:231-5
Reid, D L; Davidson, S R; Phernetton, T M et al. (1990) Adenosine causes a biphasic response in the ovine fetal placental vasculature. J Dev Physiol 13:237-40
Reid, D L; Goodfriend, T L; Hollister, M C et al. (1989) Effects of atrial natriuretic factor on maternal ovine vascular resistance. J Dev Physiol 11:25-8
Reid, D L; Hollister, M C; Davidson, S R et al. (1989) Uncoupling of excitation from contraction in uterine smooth muscle in near-term ewes. Am J Obstet Gynecol 161:229-33
Stock, M K; Reid, D L; Phernetton, T M et al. (1989) Matching of maternal and fetal flow ratios in the sheep placenta. J Dev Physiol 11:29-35
Hollister, M C; Reid, D L; Phernetton, T M et al. (1988) Dose-response curves of the uterine and placental vascular beds to prostaglandin I2. Am J Obstet Gynecol 159:1372-5
Rankin, J H; De Lone, D; Phernetton, T M (1988) Placental vascular response to prostaglandin I2 in the rabbit. J Dev Physiol 10:541-6
Rankin, J H; Landauer, M; Tian, Q et al. (1988) Forskolin dilates the maternal ovine placental vascular bed. J Dev Physiol 10:201-9
Reid, D L; Hollister, M C; Phernetton, T M et al. (1988) Effects of forskolin on placental vascular resistance in rabbits. Proc Soc Exp Biol Med 188:451-4