Vascular Effects of High-Salt After Preeclampsia

Role of the Mineralocorticoid Receptor in Microvascular Endothelial Dysfunction After Preeclampsia

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.

Study Overview

• Status: Recruiting
• Conditions: Preeclampsia; Preeclampsia Postpartum
• Intervention / Treatment: Drug: Eplerenone

• Study Type: Interventional
• Enrollment (Estimated): 40
• Phase: Early Phase 1

Contacts and Locations

• Study Contact: Name: Kelsey Schwartz, PhD; Phone Number: 319-467-1732; Email: kelsey-schwartz@uiowa.edu

Study Locations

• United States
  • Iowa
    • Iowa City, Iowa, United States, 52242
      • Recruiting
      • University of Iowa
      • Contact: Kelsey Schwartz, PhD; Phone Number: 319-467-1732; Email: kelsey-schwartz@uiowa.edu
      • Contact: Claire Goebel; Phone Number: 319-335-1914; Email: claire-goebel@uiowa.edu
      • Principal Investigator: Anna Reid-Stanhewicz, PhD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult
• Accepts Healthy Volunteers: Yes

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: High-salt supplement; Participants will be counseled to consume a low-salt diet (<2000 mg/day of sodium) for 10 days. After 3 days of a low-salt diet, participants will consume the high-salt supplement (4500 mg/day) for 7 days while maintaining a low-salt diet. On days 3 and 10, participants will arrive at the laboratory where the investigators will assess microvascular endothelial function. Blood will be collected to investigate circulating angiotensin II responses to low- (day 3) and high- (day 10) salt diet. On days 2 and 9, participants will undergo ambulatory blood pressure monitoring and 24-hour urine collection.

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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in microvascular endothelial function following local eplerenone treatment compared to placebo treatment measured by laser-Doppler flowmetry	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	Day 3 (low-salt diet run in) and Day 10 (low-salt diet + high-salt supplement)
Changes in 24-hour urine sodium	The investigators will measure urine sodium to ensure differences in salt-take between low- and high-salt.	Day 2, Day 9

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Changes in circulating aldosterone concentrations	The investigators will collect blood at the start of each experiment to determine differences in aldosterone concentrations between low- and high-salt.	Day 3, Day 10
Changes in circulating angiotensin II concentrations	The investigators will collect blood at the start of each experiment to determine differences in circulating angiotensin II concentrations between low- and high-salt.	Day 3, Day 10
Changes in ambulatory blood pressure	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.	Day 2, Day 9

Collaborators and Investigators

• Sponsor: Anna Stanhewicz, PhD
• Investigators: Principal Investigator: Anna Reid-Stanhewicz, PhD, University of Iowa

Study record dates

Study Major Dates

• Study Start (Actual): January 2, 2025
• Primary Completion (Estimated): January 15, 2027
• Study Completion (Estimated): November 15, 2027

Study Registration Dates

• First Submitted: December 19, 2024
• First Submitted That Met QC Criteria: December 19, 2024
• First Posted (Actual): December 27, 2024

Study Record Updates

• Last Update Posted (Actual): February 13, 2026
• Last Update Submitted That Met QC Criteria: February 10, 2026
• Last Verified: February 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Pregnancy Complications; Hypertension, Pregnancy-Induced; Pre-Eclampsia; Organic Chemicals; Polycyclic Compounds; Pregnanes; Steroids; Fused-Ring Compounds; Lactones; Pregnenes; Eplerenone
• Other Study ID Numbers: 202408643

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No