Pregnancy-induced hypertension (PIH) is a leading cause of maternal and fetal mortality and morbidity. The antecedents of this disease are not well resolved, and many etiologies have been proposed. Our objective is to clarify one of these, that PIH results from a defect in the regulation of sodium and volume, and assess consequent mechanisms, including changes in circulating hormones, that lead to other abnormalities seen in PIH. To accomplish this overall objective we will answer four questions:
Specific Aim #1. What is the nature of abnormalities in sodium homeostatic mechanisms in PIH? We will study pregnant women during each trimester and 4 months post partum assessing their sodium handling and volume regulation as they respond to a saline infusion and posture study while on a fixed salt intake. Additionally, hormones known to affect sodium/volume regulation will be measured. Then, these parameters will be compared to the presence of absence of PIH and its associated abnormalities.
Specific Aim #2. What are the hormonal and blood pressure responses to sodium restriction in women who have developed PIH? We will study the relative benefits of bedrest alone or bedrest plus modes salt restriction as treatments for PIH. We will seek hormonal modifications accompanying resolution of hypertension and other abnormalities of PIH to identify potential participants in the hypertensive and other pathologic processes of PIH.
Specific Aim #3. What is the status of volume and/or sodium homeostatic mechanisms in non-pregnant women with or without a history of PIH? This study will identify fixed derangements in salt handling in those women who have PIH compared to women with previous uncomplicated pregnancies to know if these abnormalities are more frequent in women having had PIH.
Specific Aim #4. What are the potential circulating factors which mediate the clinical and biochemical derangements associated with PIH? Factors known to modify sodium balance, including digitalis-like factors and thromboxane, or factors which emerge from the clinical studies as tracking with abnormal parameters and therefore having potential roles in PIH will be tested in vitro to assess their ability to produce directly or indirectly the abnormalities associated with PIH. These studies should allow us to establish whether sodium homeostatic derangements underlie, predate, and predispose women to the development of PIH, assess the efficacy of salt restriction as a treatment, and identify potential markers and mechanisms for PIH and its associated manifestations.
