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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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| High-salt supplement | Experimental | Participants will be counseled to consume a low-salt diet (<2000 mg/day of sodium) for 10 days. After 3 days of a low-salt diet, participants will consume the high-salt supplement (4500 mg/day) for 7 days while maintaining a low-salt diet. On days 3 and 10, participants will arrive at the laboratory where the investigators will assess microvascular endothelial function. Blood will be collected to investigate circulating angiotensin II responses to low- (day 3) and high- (day 10) salt diet. On days 2 and 9, participants will undergo ambulatory blood pressure monitoring and 24-hour urine collection. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Eplerenone | Drug | 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. |
| Measure | Description | Time Frame |
|---|---|---|
| Change in microvascular endothelial function following local eplerenone treatment compared to placebo treatment measured by laser-Doppler flowmetry | Cutaneous vascular vasodilator response (cutaneous conductance; %max) to local heating of the skin; intradermal microdialysis for the local delivery of eplerenone compared to control (Ringer's solution), followed by L-NAME infusion to quantify NO-dependent response | Day 3 (low-salt diet run in) and Day 10 (low-salt diet + high-salt supplement) |
| Changes in 24-hour urine sodium | The investigators will measure urine sodium to ensure differences in salt-take between low- and high-salt. | Day 2, Day 9 |
| Measure | Description | Time Frame |
|---|---|---|
| Changes in circulating aldosterone concentrations | The investigators will collect blood at the start of each experiment to determine differences in aldosterone concentrations between low- and high-salt. | Day 3, Day 10 |
| Changes in circulating angiotensin II concentrations |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Kelsey Schwartz, PhD | Contact | 319-467-1732 | kelsey-schwartz@uiowa.edu |
| Name | Affiliation | Role |
|---|---|---|
| Anna Reid-Stanhewicz, PhD | University of Iowa | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| University of Iowa | Recruiting | Iowa City | Iowa | 52242 | United States |
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| ID | Term |
|---|---|
| D011225 | Pre-Eclampsia |
| ID | Term |
|---|---|
| D046110 | Hypertension, Pregnancy-Induced |
| D011248 | Pregnancy Complications |
| D005261 | Female Urogenital Diseases and Pregnancy Complications |
| D000091642 | Urogenital Diseases |
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| ID | Term |
|---|---|
| D000077545 | Eplerenone |
| ID | Term |
|---|---|
| D007783 | Lactones |
| D009930 | Organic Chemicals |
| D011283 | Pregnenes |
| D011278 | Pregnanes |
| D013256 |
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The investigators will collect blood at the start of each experiment to determine differences in circulating angiotensin II concentrations between low- and high-salt. |
| Day 3, Day 10 |
| Changes in ambulatory blood pressure | The investigators will measure ambulatory blood pressure, assessed as mean arterial pressure calculated from measured systolic and diastolic pressures, responses to low- and high-salt. | Day 2, Day 9 |
| Steroids |
| D000072473 | Fused-Ring Compounds |
| D011083 | Polycyclic Compounds |