Preeclampsia, Preeclampsia Postpartum
Conditions
Brief summary
Women who develop preeclampsia during pregnancy are more likely to develop and die of cardiovascular disease later in life, even if they are otherwise healthy. Importantly, women who had preeclampsia have an exaggerated vascular responsiveness to hypertensive stimuli, such as high-salt intake, compared to women who had a healthy pregnancy. The reason why this occurs is unclear but may be related to impaired endothelial function and dysregulation of the angiotensin system that occurs during the preeclamptic pregnancy and persists postpartum, despite the remission of clinical symptoms. While the association between a history of preeclampsia and vascular dysfunction leading to elevated CVD risk is well known, the mechanisms underlying this dysfunction remains unclear. The purpose of this study is to examine the role of vascular mineralocorticoid receptor, the terminal receptor in the angiotensin system that contributes to blood pressure regulation, in mediating exaggerated microvascular endothelial dysfunction before and after a high-salt stimulus. This will help us better understand the mechanisms of microvascular dysfunction these women, and how inhibition of these receptors may improve microvascular function. In this study, we use the blood vessels in the skin as a representative vascular bed for examining mechanisms of microvascular dysfunction in humans. Using a minimally invasive technique (intradermal microdialysis for the local delivery of pharmaceutical agents) we examine the blood vessels in a nickel-sized area of the skin.
Interventions
DRUGEplerenone
Local heating: eplerenone is locally and acutely delivered to the cutaneous microvasculature during local heating of the skin to assess endothelium-dependent dilation, L-NAME is added to assess nitric oxide-dependent dilation during this response.
Sponsors
Anna Stanhewicz, PhD
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
BASIC_SCIENCE
Masking
NONE
Eligibility
Sex/Gender
FEMALE
Age
18 Years to 45 Years
Healthy volunteers
Yes
Inclusion criteria
* women who had preeclampsia and women who did not have preeclampsia * 12 weeks to 5 years postpartum * 18-45 years old
Exclusion criteria
* history of hypertension or metabolic disease before pregnancy * history of gestational diabetes * history of gestational hypertension without preeclampsia * skin diseases * current tobacco use * current antihypertensive medication * statin or other cholesterol-lowering medication * currently pregnant * body mass index less than 18.5 kg/m2 * allergy to materials used during the experiment.(e.g. latex), * known allergy to study drugs or salt-supplement
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in microvascular endothelial function following local eplerenone treatment compared to placebo treatment measured by laser-Doppler flowmetry | Day 3 (low-salt diet run in) and Day 10 (low-salt diet + high-salt supplement) | Cutaneous vascular vasodilator response (cutaneous conductance; %max) to local heating of the skin; intradermal microdialysis for the local delivery of eplerenone compared to control (Ringer's solution), followed by L-NAME infusion to quantify NO-dependent response |
| Changes in 24-hour urine sodium | Day 2, Day 9 | The investigators will measure urine sodium to ensure differences in salt-take between low- and high-salt. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Changes in circulating aldosterone concentrations | Day 3, Day 10 | The investigators will collect blood at the start of each experiment to determine differences in aldosterone concentrations between low- and high-salt. |
| Changes in circulating angiotensin II concentrations | Day 3, Day 10 | The investigators will collect blood at the start of each experiment to determine differences in circulating angiotensin II concentrations between low- and high-salt. |
| Changes in ambulatory blood pressure | Day 2, Day 9 | The investigators will measure ambulatory blood pressure, assessed as mean arterial pressure calculated from measured systolic and diastolic pressures, responses to low- and high-salt. |
Countries
United States
Contacts
CONTACTKelsey Schwartz, PhD
PRINCIPAL_INVESTIGATORAnna Reid-Stanhewicz, PhD
University of Iowa
Outcome results
None listed