Angiotensin II and Chronic Inflammation in Persistent Microvascular Dysfunction Following Preeclampsia

Early Phase 1

Completed

Brief Summary: Women who develop preeclampsia during pregnancy are more likely to develop cardiovascular disease later in life, even if they are otherwise healthy. The reason why this occurs is unclear but may be related to blood vessel damage and increased inflammation that occurs during the preeclamptic pregnancy and persists postpartum. The purpose of this investigation is to 1) determine the mechanisms contributing to this lasting blood vessel damage and chronic inflammation, and to 2) identify factors (both physiological and pharmacological) that mitigate these negative effects in order to inform better clinical management of cardiovascular disease risk in women who have had preeclampsia.

Recruitment & Eligibility

Inclusion Criteria

Post-partum women who have delivered within two years and who have had a preeclamptic pregnancy diagnosed by their obstetrician before 34 weeks of gestation and confirmed according to the American College of Obstetricians and Gynecologists criteria for severe preeclampsia. [This information will be self-reported by the subjects.]
Post-partum women who have delivered within two years and who have had a normal pregnancy.
18 years and older.

Exclusion Criteria

skin diseases
current tobacco use
diagnosed or suspected hepatic or metabolic disease
statin or other cholesterol-lowering medication
history of hypertension prior to pregnancy
history of gestational diabetes
current pregnancy
allergy to aspirin or NSAIDs or known allergy to materials used during the experiment (e.g. latex)
renal disease, bleeding disorders and history of gastrointestinal bleeding.
Known allergies to study drugs
Taking blood thinners, aspirin or NSAIDS.
Women who choose to breastfeed will not participate in any parts of the project that include salsalate.

Arm && Interventions

Group	Intervention	Description
Placebo	Placebo Oral Tablet	-
Salsalate	Salsalate Oral Tablet	-

Primary Outcome Measures

Name	Time	Method
Microvascular Endothelial Function (Cutaneous Conductance, %Maximum)	immediately following the 4 days or oral treatment (salsalate or placebo)	Endothelium-dependent vasodilation assessed as cutaneous conductance response (cutaneous conductance = local red blood cell flux/mean arterial pressure; %maximum) to exogenous acetylcholine delivered via intradermal microdialysis.

Secondary Outcome Measures

Name	Time	Method
Peripheral Blood Mononuclear Cell Inflammatory Response to Ang II	at the completion of 4 days of oral (placebo or salsalate) treatment	inflammatory cytokine (TNFalpha) release by peripheral blood mononuclear cells isolated from fresh whole blood collected via venipuncture and stimulated with angiotensin II ex vivo.

Locations (2): University of Iowa
🇺🇸
Iowa City, Iowa, United States
Pennsylvania State University
🇺🇸
University Park, Pennsylvania, United States
University of Iowa
🇺🇸Iowa City, Iowa, United States