Lysine-specific Demethylase 1 and Salt-sensitivity in Humans

Study Overview
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Brief Summary
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The purpose of this study is to investigate the role dietary salt plays in epigenetic regulation of blood pressure, focusing on the salt-sensitive regulatory enzyme Lysine-specific demethylase 1.

Detailed Description
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The purpose of this study is to investigate the role dietary salt plays in epigenetic regulation of blood pressure in African American and Caucasians, focusing on the salt-sensitive regulatory enzyme Lysine-specific demethylase 1. This might help us understand why some people develop high blood pressure. Healthy volunteers will be screened for eligibility and invited to participate in a 2 weeks study. Week 1 will be consumption of a low salt diet. Week 2 will be a high salt diet. At the end of each week, participants will be admitted to a Clinical Research Center overnight and for one day. On the CRC, participants will remain fasting and supine overnight and then next morning undergo hormonal and vascular testing. This will consist of blood drawing, echocardiogram, vascular tonometry, and assessment of renal blood flow before and after a low-dose Angiotensin II infusion. The study outcome will compare how variants in the LSD1 gene affect hormonal and vascular responses according to race. This information will help us determine why some races and genetic profiles are more susceptible to detrimental effects of salt in the diet while others are protected against these effects.

Official Title
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Lysine-specific Demethylase 1 and Salt-sensitivity in Humans

Conditions
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Healthy Subjects

Intervention / Treatment
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* Other: Aldosterone response to AngII LS
* Other: Renal blood flow response to salt
* Other: Vascular Stiffness


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age 25-45 years Caucasian or African American No gender preference (anticipate 50% female) Normotensive (screening blood pressure <140/90 mmHg) No history of hypertension, diabetes, stroke, coronary artery disease, kidney disease, cancer, thyroid disease, preeclampsia, or hospitalizations in 6 months Normal screening laboratory values (CMP, TSH, A1c) Normal ECG BMI <25 kg/m2 Exclusion Criteria: Pregnancy Breast feeding Any medication or herbal preparation >6oz alcohol/week Tobacco use Illicit drug use Chronic NSAID use Recent steroid use (injected, inhaled, oral) Decongestant use in the past 2 weeks Known sensitivity to infused Angiotensin II or para-amino hippurate

Ages Eligible for Study
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Minimum Age: 25 Years
Maximum Age: 45 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Other
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Heathy volunteers
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Afr-Amer risk allele<br>African Americans carrying the LSD1 affected allele | Other: Aldosterone response to AngII LS<br>* Change in aldosterone from baseline to after Ang II infusion on a LS diet<br>Other: Renal blood flow response to salt<br>* Change in renal blood flow: High salt to low salt diet<br>Other: Vascular Stiffness<br>* Change in vascular stiffness, baseline compared to AngII<br>|
| Placebo Comparator: Cauc risk allele<br>Caucasians carrying the LSD1 affected allele | Other: Aldosterone response to AngII LS<br>* Change in aldosterone from baseline to after Ang II infusion on a LS diet<br>Other: Renal blood flow response to salt<br>* Change in renal blood flow: High salt to low salt diet<br>Other: Vascular Stiffness<br>* Change in vascular stiffness, baseline compared to AngII<br>|
| Placebo Comparator: Afr-Amer non-risk allele<br>African Americans carrying the LSD1 non-risk allele | Other: Aldosterone response to AngII LS<br>* Change in aldosterone from baseline to after Ang II infusion on a LS diet<br>Other: Renal blood flow response to salt<br>* Change in renal blood flow: High salt to low salt diet<br>Other: Vascular Stiffness<br>* Change in vascular stiffness, baseline compared to AngII<br>|
| Placebo Comparator: Cauc non-risk allele<br>Caucasians carrying the LSD1 non-risk allele | Other: Aldosterone response to AngII LS<br>* Change in aldosterone from baseline to after Ang II infusion on a LS diet<br>Other: Renal blood flow response to salt<br>* Change in renal blood flow: High salt to low salt diet<br>Other: Vascular Stiffness<br>* Change in vascular stiffness, baseline compared to AngII<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Aldosterone response to angiotensin II | Change in aldosterone, baseline to after angiotensin II by genotype/race | After 1 week dietary salt manipulation | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Renal blood flow response to dietary salt | Change in renal blood flow, high salt diet to low salt diet by genotype/race | After 1 week dietary salt manipulation on both diets | 
| Vascular stiffness response to angiotensin II | Change in vascular stiffness, baseline to after angiotensin II by genotype/race | After 1 week dietary salt manipulation |