Balance of Angiotensin II Receptors in Vessel Function After Preeclampsia

Otherwise healthy women who develop preeclampsia during pregnancy are more likely to develop and die of cardiovascular disease later in life. The reason why this occurs is unclear but may be related to impaired endothelial function and dysregulation of the angiotensin system that occurs during preeclampsia and persists postpartum, despite the remission of clinical symptoms. The purpose of this investigation is to determine the mechanisms contributing to this lasting blood vessel damage caused by reduced endothelial function in women who have had preeclampsia compared to women who had a healthy pregnancy. Identification of these mechanisms and treatment strategies may lead to better clinical management of cardiovascular disease risk in these women.

The purpose of this study is to examine differences in the microvascular balance of angiotensin II receptors women who have had preeclampsia. This will help the investigators better understand the mechanisms of dysregulated angiotensin II receptors in formerly preeclamptic women, and how activation or inhibition of these receptors may restore microvascular function.

In this study, the investigators 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) the investigators examine the blood vessels in a dime-sized area of the skin.

Study Overview

• Status: Completed
• Conditions: Preeclampsia
• Intervention / Treatment: Drug: Compound 21; Drug: Angiotensin II

• Study Type: Interventional
• Enrollment (Actual): 24
• Phase: Early Phase 1

Contacts and Locations

Study Locations

• United States
  • Iowa
    • Iowa City, Iowa, United States, 52242
      • University of Iowa

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 or gestational hypertension
• skin diseases
• current tobacco use
• current antihypertensive medication
• statin or other cholesterol-lowering medication
• currently pregnant or planning to become pregnant
• body mass index less than <18.5 or >30 kg/m2
• allergy to materials used during the experiment.(e.g. latex),
• known allergy to study drugs

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Other: History of a preeclampsia; Women who had preeclampsia in their most recent pregnancy	Drug: Compound 21; differences in vasodilation to compound 21 in the skin between groups; Drug: Angiotensin II; differences in vasoconstriction to angiotensin II in the skin between groups
Other: History of a healthy pregnancy; Women who had an uncomplicated pregnancy	Drug: Compound 21; differences in vasodilation to compound 21 in the skin between groups; Drug: Angiotensin II; differences in vasoconstriction to angiotensin II in the skin between groups

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in microvascular angiotensin II (ang II) type 2 receptor (AT2R)-mediated dilation response measured by laser-Doppler flowmetry	cutaneous vascular vasodilator responses to compound 21 perfusion in lactated Ringer's and losartan treated microdialysis sites	at the study visit, an average of 4 hours
Change in microvascular ang II-mediated constriction response measured by laser-Doppler flowmetry	cutaneous vascular vasoconstrictor responses to angiotensin II perfusion in lactated Ringer's and PD-123319 treated microdialysis sites	at the study visit, an average of 4 hours

Collaborators and Investigators

• Sponsor: Anna Stanhewicz, PhD

Study record dates

Study Major Dates

• Study Start (Actual): December 8, 2023
• Primary Completion (Actual): October 24, 2024
• Study Completion (Actual): December 10, 2024

Study Registration Dates

• First Submitted: November 27, 2023
• First Submitted That Met QC Criteria: December 4, 2023
• First Posted (Actual): December 6, 2023

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: December 19, 2024
• Last Verified: December 1, 2024

More Information

Terms related to this study

• Keywords: postpartum; vascular
• Additional Relevant MeSH Terms: Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Pregnancy Complications; Hypertension, Pregnancy-Induced; Pre-Eclampsia; Molecular Mechanisms of Pharmacological Action; Anti-Inflammatory Agents; Protease Inhibitors; Enzyme Inhibitors; Serine Proteinase Inhibitors; Vasoconstrictor Agents; Giapreza; Compound 21; Angiotensin II; Angiotensinogen
• Other Study ID Numbers: 202309383

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