Vascular Effects of High-Salt After Preeclampsia

Официальное название

Role of the Mineralocorticoid Receptor in Microvascular Endothelial Dysfunction After Preeclampsia

Обзор

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. Importantly, women who had preeclampsia have an exaggerated vascular responsiveness to hypertensive stimuli, such as high-salt intake, compared to women who had a healthy pregnancy. 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. While the association between a history of preeclampsia and vascular dysfunction leading to elevated CVD risk is well known, the mechanisms underlying this dysfunction remains unclear. The purpose of this study is to examine the role of vascular mineralocorticoid receptor, the terminal receptor in the angiotensin system that contributes to blood pressure regulation, in mediating exaggerated microvascular endothelial dysfunction before and after a high-salt stimulus. This will help us better understand the mechanisms of microvascular dysfunction these women, and how inhibition of these receptors may improve 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 nickel-sized area of the skin.

Вмешательства

• Препарат Eplerenone
  Local heating: eplerenone 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.

Первичные конечные точки

• Change in microvascular endothelial function following local eplerenone treatment compared to placebo treatment measured by laser-Doppler flowmetry [Срок оценки: Day 3 (low-salt diet run in) and Day 10 (low-salt diet + high-salt supplement)]
• Changes in 24-hour urine sodium [Срок оценки: Day 2, Day 9]

Вторичные конечные точки (3)

• Changes in circulating aldosterone concentrations [Срок оценки: Day 3, Day 10]
• Changes in circulating angiotensin II concentrations [Срок оценки: Day 3, Day 10]
• Changes in ambulatory blood pressure [Срок оценки: Day 2, Day 9]

Критерии участия

Критерии включения

• women who had preeclampsia and women who did not have preeclampsia
• 12 weeks to 5 years postpartum
• 18-45 years old

Критерии исключения

• history of hypertension or metabolic disease before pregnancy
• history of gestational diabetes
• history of gestational hypertension without preeclampsia
• skin diseases
• current tobacco use
• current antihypertensive medication
• statin or other cholesterol-lowering medication
• currently pregnant
• body mass index less than 18.5 kg/m2
• allergy to materials used during the experiment.(e.g. latex),
• known allergy to study drugs or salt-supplement

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Да

Дизайн исследования

Распределение

Не применимо

Модель

Одна группа

Маскирование

Открытое

Основная цель

Фундаментальное исследование

Центры проведения

США · 1 центр

• University of Iowa — Iowa City

Идентификаторы

NCT: NCT06749418 · 202408643

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

Открыть это исследование на ClinicalTrials.gov ↗