Balance of Angiotensin II Receptors in Vessel Function After Preeclampsia

Study Overview
=================
Brief Summary
-----------------
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 us better understand the mechanisms of dysregulated angiotensin II receptors in these women, and how activation or inhibition of these receptors may restore 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 dime-sized area of the skin.

Official Title
-----------------
Balance of Angiotensin II Receptors in Vessel Function After Preeclampsia

Conditions
-----------------
Preeclampsia

Intervention / Treatment
-----------------
* Drug: Compound 21
* Drug: Angiotensin II


Participation Criteria
=================
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 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

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 45 Years

Sexes Eligible for Study
-----------------
Female

Accepts Healthy Volunteers
-----------------
Accepts Healthy Volunteers

Study Plan
=================
How is the study designed?
-----------------

Design Details

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


Arms and Interventions

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

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 | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
postpartum, vascular