Sensitivity of Angiotensin II Type II Receptors in Women Following Preeclampsia

Trial statusRecruiting
Trial phaseEarly Phase 1
Trial typeInterventional
Biological sexFemale
Age18-45
SponsorAnna Stanhewicz, PhD

About this trial

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. 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. 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 the microvascular differences in women who have had preeclampsia following activation of protective angiotensin receptors in the skin. This will help increase understanding of the mechanisms of angiotensin II receptors in these women, and how activation 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.

Eligibility criteria

This trial accepts healthy volunteers

Qualifiers

women who had preeclampsia and women who did not have preeclampsia

12 weeks to 5 years postpartum

18-45 years old

Disqualifiers

history of hypertension or metabolic disease before pregnancy

history of gestational diabetes

skin diseases

current tobacco use

Trial design

Design model

Single group

Treatments tested in this trial

  • Compound 21

    Drug

    AT2R sensitivity: compound 21, and compound 21+ L-NAME (nitric oxide synthase inhibitor) are locally and acutely delivered to the cutaneous microvasculature to assess AT2R-mediated dilation and role of nitric oxide in this response Local heating: compound 21 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

Treatment groups

30 Participants
are divided into 1 treatment group
Group A: assessment of microvascular functionExperimental treatment 1 intervention

Trial outcomes

Primary outcomes

1

Change in microvascular blood flow response to local compound 21 treatment measured by laser-Doppler flowmetry

Cutaneous vascular vasodilator response (cutaneous conductance; %max) to exogenous compound 21 perfusion; intradermal microdialysis for the local delivery of compound 21

Time frame
post 1 hour of skin perfusion
2

Change in microvascular endothelial function following local C21 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 compound 21 compared to control (Ringer's solution), followed by L-NAME infusion to quantify NO-dependent response

Time frame
post 1 hour of skin perfusion

Secondary outcomes

1

Angiotensin receptor expression in endothelial cells

Quantify expression of angiotensin II receptor expression in biopsied endothelial cells

Time frame
a total of 1 time during the study, within ~4 weeks following enrollment

Other outcomes

Sponsors and contacts

Click on the lead sponsor to view all of their trials.

Anna Stanhewicz, PhD

Lead sponsor

University of Iowa

Sponsor institution