The mechanisms responsible for normal maternal cardiovascular adaptation during pregnancy and the alterations in these mechanisms that occur in hypertensive pregnancies are not well understood. There is considerable evidence, however, that prostanoids may be involved since the PGI2/TxA2 ratio is elevated in normal pregnancy and reduced in pregnancies complicated by hypertension. Furthermore, inhibition of prostaglandin production in women and animals has profound effects on the reactivity of the systemic and uterine vascular beds to vasoconstriction by angiotensin 11 and alpha-adrenergic agents. Therefore, the long-term objectives of this project are to determine if the vascular alterations observed in hypertensive pregnancies (preeclampsia/chronic hypertension) are coincident with (or caused by) the alterations in PGI2 and TxA2 production, and what are the resulting cellular and intracellular events. To address this we will utilize in vitro studies of maternal systemic and uterine and fetal placental arteries as well as in vivo studies of the mechanism by which low-dose aspirin treatment affects the progress and maternal and fetal outcomes of hypertensive pregnancies. Using these methods we will define in detail the role of prostaglandins and related cellular events in the control of in vivo vascular reactivity to angiotensin II, in addition to in vitro reactivity to angiotensin II, alpha-adrenergic agents and KCI. The in vitro studies will encompass the effects of these agents on prostaglandin production, calcium and calcium channels, cAMP generation, phosphatidylinositol hydrolysis, and the activity of protein kinase A and C. Studies to examine angiotensin II and alpha1- and alpha2 -adrenergic receptor number and affinity as well as studies of the structural and compliance changes that occur in the arteries of normal and hypertensive pregnant women also are described. By achieving these aims our understanding of normal pregnancy adaptation and the alterations associated with pregnancy-induced hypertension (preeclampsia) will be better understood, thereby improving methods of care for women with this disease.

Project Start
1988-06-01
Project End
1993-05-31
Budget Start
1988-06-01
Budget End
1989-05-31
Support Year
1
Fiscal Year
1988
Total Cost
Indirect Cost
Name
University of Texas Sw Medical Center Dallas
Department
Type
Schools of Medicine
DUNS #
City
Dallas
State
TX
Country
United States
Zip Code
75390
Magness, R R; Gant, N F (1994) Control of vascular reactivity in pregnancy: the basis for therapeutic approaches to prevent pregnancy-induced hypertension. Semin Perinatol 18:45-69
North, A J; Brannon, T S; Wells, L B et al. (1994) Hypoxia stimulates prostacyclin synthesis in newborn pulmonary artery endothelium by increasing cyclooxygenase-1 protein. Circ Res 75:33-40
Brannon, T S; North, A J; Wells, L B et al. (1994) Prostacyclin synthesis in ovine pulmonary artery is developmentally regulated by changes in cyclooxygenase-1 gene expression. J Clin Invest 93:2230-5
Ramin, S M; Ramin, K D; Cox, K et al. (1994) Comparison of prophylactic angiotensin II versus ephedrine infusion for prevention of maternal hypotension during spinal anesthesia. Am J Obstet Gynecol 171:734-9
Shaul, P W; Wells, L B (1994) Oxygen modulates nitric oxide production selectively in fetal pulmonary endothelial cells. Am J Respir Cell Mol Biol 11:432-8
Magness, R R; Rosenfeld, C R (1993) Calcium modulation of endothelium-derived prostacyclin production in ovine pregnancy. Endocrinology 132:2445-52
Shaul, P W; Farrar, M A; Magness, R R (1993) Pulmonary endothelial nitric oxide production is developmentally regulated in the fetus and newborn. Am J Physiol 265:H1056-63
Maki, N; Magness, R R; Miyaura, S et al. (1993) Platelet-activating factor-acetylhydrolase activity in normotensive and hypertensive pregnancies. Am J Obstet Gynecol 168:50-4
Hoffman, D R; Favour, S; Uauy, R et al. (1993) Distribution of unsaturated fatty acids in phospholipids of arteries from nonpregnant, pregnant and fetal sheep. Prostaglandins Leukot Essent Fatty Acids 49:907-14
Shaul, P W; Farrar, M A; Magness, R R (1993) Oxygen modulation of pulmonary arterial prostacyclin synthesis is developmentally regulated. Am J Physiol 265:H621-8

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