Losartan for Improved Vascular Endothelial Function After Preeclampsia (LIVE-PE)

Angiotensin II Receptor Inhibition to Improve Microvascular Function in Women Who Have Had 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. 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 determine the mechanisms contributing to this lasting blood vessel damage and to test whether taking a medication that blocks angiotensin II receptors (losartan) decrease these negative effects in women who have had preeclampsia. Identification of these mechanisms and treatment strategies may lead to better clinical management,of cardiovascular disease risk in these women. In this study we use the blood vessels in the skin as a representative vascular bed. Using a minimally invasive technique (intradermal microdialysis for the local delivery of pharmaceutical agents) we examine the blood vessels in a nickle-sized area of the skin in women who have had preeclampsia. We make these measurements after the subjects take a placebo and after they take losartan (an angiotensin II receptor blocker) to test whether this treatment improves vascular function in these women. As a compliment to these measurements, we also draw blood from the subjects and isolate the inflammatory cells to test how sensitive their inflammatory responses are following the placebo and the losartan treatment.

cutaneous vascular vasodilator response to exogenous acetylcholine perfusion; measured with laser-Doppler flowmetry coupled with intradermal microdialysis delivery of acetylcholine alone or co-infused with L-NAME

cutaneous vascular vasodilator response to exogenous acetylcholine perfusion; measured with laser-Doppler flowmetry coupled with intradermal microdialysis delivery of acetylcholine alone or co-infused with L-NAME

cutaneous vascular constrictor response to exogenous ang II perfusion; measured by laser-Doppler flowmetry coupled with intradermal microdialysis delivery of angiotensin II

at the completion of 6 weeks of oral losartan treatment, and 2) at the completion of 6 weeks of placebo treatment

cutaneous vascular constrictor response to exogenous ang II perfusion; measured by laser-Doppler flowmetry coupled with intradermal microdialysis delivery of angiotensin II

carotid-femoral and carotid-brachial Pulse Wave velocity; measured by applanation tonometry using the Sphygmocor pulse wave analysis system

carotid-femoral and carotid-brachial Pulse Wave velocity; measured by applanation tonometry using the Sphygmocor pulse wave analysis system

a total of 2 times throughout the study: 1) at the completion of 6 weeks of oral losartan treatment, and 2) at the completion of 6 weeks of placebo treatment

isolated peripheral blood mononuclear cell inflammatory responses to ang II and LPS; measured by assessing inflammatory cytokines (ELISA) in cell culture supernatants collected from PBMCs treated with ang II or LPS for 24 hours

a total of 2 times throughout the study: 1) at the completion of 6 weeks of oral losartan treatment, and 2) at the completion of 6 weeks of placebo treatment

Inclusion Criteria: Post-partum women, 18 years or older, who have delivered within 24 months of the study visit who have had a preeclamptic pregnancy diagnosed by their obstetrician and confirmed according to the American College of Obstetricians and Gynecologists criteria for preeclampsia. [This information will be self-reported by the subjects.] Using an effective method of birth control and not planning to become pregnant in the next 6 months. Exclusion Criteria: skin diseases, current tobacco use, diagnosed or suspected hepatic or metabolic disease including chronic kidney disease (CKD) defined as reduced eGFR < 60 mL/min/1.73m2, statin or other cholesterol-lowering medication, current antihypertensive medication, history of hypertension prior to pregnancy, history of gestational diabetes, current pregnancy or breastfeeding, body mass index <18.5 kg/m2, allergy to materials used during the experiment.(e.g. latex), known allergies to study drugs.