Vascular Effects of High-Salt After Preeclampsia

Official title

Role of the Mineralocorticoid Receptor in Microvascular Endothelial Dysfunction After Preeclampsia

Overview

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

• Drug Eplerenone
  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.

Primary outcome measures

• Change in microvascular endothelial function following local eplerenone treatment compared to placebo treatment measured by laser-Doppler flowmetry [Time frame: Day 3 (low-salt diet run in) and Day 10 (low-salt diet + high-salt supplement)]
• Changes in 24-hour urine sodium [Time frame: Day 2, Day 9]

Secondary outcome measures (3)

• Changes in circulating aldosterone concentrations [Time frame: Day 3, Day 10]
• Changes in circulating angiotensin II concentrations [Time frame: Day 3, Day 10]
• Changes in ambulatory blood pressure [Time frame: Day 2, Day 9]

Eligibility criteria

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

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: Yes

Study design

Allocation

N/A

Model

Single group

Masking

Open label

Primary purpose

Basic science

Study locations

United States · 1 center

• University of Iowa — Iowa City

Identifiers

NCT: NCT06749418 · 202408643

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗