Preeclampsia is a devastating disorder of pregnancy characterized by high blood pressure, proteinuria, headache, renal glomerular endotheliosis, multi-organ system failure, and fetal and maternal demise. As reviewed in Chapter I, not much is known about the pathogenesis of preeclampsia, contributing to a lack of biomarkers and treatments for the disease. In Chapter II, we review arginine vasopressin, a circulating neuropeptide hormone with important fluid balance and cardiovascular actions. Vasopressin binds to numerous receptors throughout the body to elicit its effects and is associated with various disease states. In Chapter III, we discuss evidence for vasopressin as an etiology of preeclampsia. Specifically, that vasopressin secretion is elevated very early in pregnancies affected by preeclampsia and infusion of vasopressin into pregnant C57BL/6J mice causes physiological features similar to those seen in preeclampsia. In Chapter IV, we show that vasopressin administration during mouse pregnancy models specific subtypes of preeclampsia through time- and receptor-specific mechanisms. The role of angiotensin 1a receptors on vasopressin-producing cells in fluid homeostasis is shown in Chapter V and their role in metabolism is depicted in Chapter VI. Overall, we conclude that vasopressin is an important mediator of features of preeclampsia and that angiotensin 1a receptors on vasopressin-producing cells are important for normal fluid homeostasis.
Vasopressin in preeclampsia
Abstract
Details
- Title: Subtitle
- Vasopressin in preeclampsia
- Creators
- Jeremy Anton Sandgren - University of Iowa
- Contributors
- Justin L. Grobe (Advisor)Rory A. Fisher (Committee Member)Kamal Rahmouni (Committee Member)Mark K. Santillan (Committee Member)Curt D. Sigmund (Committee Member)
- Resource Type
- Dissertation
- Degree Awarded
- Doctor of Philosophy (PhD), University of Iowa
- Degree in
- Pharmacology
- Date degree season
- Spring 2019
- DOI
- 10.17077/etd.89nm-lx8g
- Publisher
- University of Iowa
- Number of pages
- xi, 165 pages
- Copyright
- Copyright © 2019 Jeremy Anton Sandgren
- Language
- English
- Description illustrations
- color illustrations
- Description bibliographic
- Includes bibliographical references (pages 144-165).
- Public Abstract (ETD)
Preeclampsia is a devastating disorder of pregnancy characterized by high blood pressure, proteinuria, headache, renal glomerular endotheliosis, multi-organ system failure, and fetal and maternal demise. Currently, the only treatment for preeclampsia is fetal and placental delivery, which frequently results in emergent preterm delivery. Unfortunately, little is known about the pathogenesis of preeclampsia, contributing to a lack of biomarkers and new treatments for this disease.
We and others recently discovered that a circulating hormone called vasopressin is elevated very early in pregnancies of women who go on to develop preeclampsia. Additionally, when vasopressin is infused throughout mouse pregnancies, they develop specific physiological features of preeclampsia. Here we find that preventing vasopressin action on specific receptors at specific times of gestation prevents onset of disease in this mouse model, providing a template for the development of future therapeutics. Furthermore, we identify receptors on cells that secrete vasopressin that are important for fluid homeostasis, a process that may be dysfunctional in preeclampsia.
- Academic Unit
- Neuroscience and Pharmacology
- Record Identifier
- 9983776779702771