Prenatal Aspirin and Postpartum Vascular Function

Protective Mechanisms of Prenatal Aspirin Therapy on Maternal Vascular Dysfunction Following Preeclampsia

Preeclampsia is a pregnancy disorder affecting ~5-10% of pregnancies in the United States. 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. Low dose aspirin (LDA; 75-150mg/daily) is currently the most effective and clinically accepted therapy for reducing preeclampsia prevalence in women at high risk for developing the syndrome. The purpose of this study is to interrogate the mechanisms by which LDA therapy mitigates persistent vascular dysfunction in postpartum women who have had preeclampsia. 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) they examine the blood vessels in a dime-sized area of the skin in women who have had a history of preeclampsia. As a compliment to these measurements, they also draw blood from the subjects and isolate the inflammatory cells.

The investigators use intradermal microdialysis to deliver acetylcholine, acetylcholine + L-NAME, endothelin-1, endothelin-1 + BQ-788, and endothelin-1 + BQ-123 to the cutaneous microvasculature.

acetylcholine, and acetylcholine + L-NAME (Nitric oxide synthase inhibitor) are locally and acutely delivered to the cutaneous microvasculature to assess endothelium- and nitric oxide-dependent dilation

endothelin-1, endothelin-1 + BQ-788 (endothelin receptor type B-inhibitor), and endothelin-1 + BQ-123 (endothelin receptor type A-inhibitor) are locally and acutely delivered to the cutaneous microvasculature to assess endothelin-mediated constriction and the role of the receptor subtypes in this response.

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 response to exogenous endothelin-1 perfusion; measured with laser-Doppler flowmetry coupled with intradermal microdialysis delivery of endothelin-1 alone or co-infused with BQ-788 or BQ-123

Inclusion: 18 years or older, 12 weeks to 5 years postpartum and one of the following: women who had a normal pregnancy and did not use low does aspirin (LDA) during pregnancy, women who had a normal pregnancy and used LDA during pregnancy, women who had preeclampsia and did not use LDA during pregnancy, women who had preeclampsia and used LDA during pregnancy. Exclusion: current daily aspirin use, 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, body mass index <18.5 kg/m2, allergy to materials used during the experiment.(e.g. latex), known allergies to study drugs.