Adverse Neurogenic Actions of Dietary Salt

Study Overview
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Brief Summary
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Excess dietary salt increases the risk for cardiovascular events, even in people that are not hypertensive. There is some evidence that excess dietary salt exaggerates blood pressure and sympathetic nervous system responses to various perturbations and increases blood pressure variability. This proposal will examine the effects of low, medium, and high salt diets on cardiovascular reactivity and blood pressure variability.

Detailed Description
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Excess dietary salt causes target organ damage and increases the risk for adverse cardiovascular (CV) events independent of blood pressure (BP). Recent data in salt-resistant, normotensive rodents suggest that high dietary salt enhances the excitability or gain of sympathetic circuits, exaggerates sympathetic and CV responses to various stimuli, and increases BP variability (BPV). There are limited data regarding the impact of dietary salt intake on sympathetic nerve activity (SNA) and CV function in salt-resistant humans as well as the underlying mechanisms contributing to these adverse effects. The long-term goal is to determine how dietary salt adversely affects BP regulation and CV health. The objective of this proposal is to comprehensively evaluate the impact of dietary salt intake on SNA and CV reactivity and BPV in normotensive humans. The investigators have 2 specific aims: 1) Aim 1 will test the hypothesis that high dietary salt increases SNA and CV reactivity in normotensive adults, 2) Aim 2 will test the hypothesis that high dietary salt increases BPV in normotensive adults. The expected outcome is to demonstrate that dietary salt loading increases CV reactivity and BPV through a sympathetic nervous system mechanism that originates in the brain. The proposed research is significant, as these studies will provide empirical evidence that dietary salt intake impacts neurohumoral control of the circulation in salt-resistant humans. The proposed research is innovative because it will identify a novel neurogenic action of dietary salt in human CV regulation.

Official Title
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Adverse Neurogenic Actions of Dietary Salt

Conditions
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Blood Pressure

Intervention / Treatment
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* Other: Low Sodium Diet
* Other: Medium Sodium Diet
* Other: High Sodium Diet


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: normal blood pressure men, Women, minorities ECG within normal limits screening blood panel within normal limits Exclusion Criteria: high blood pressure (>140/90 mmHg) history of cardiovascular disease history of cancer history of diabetes history of kidney disease obesity (BMI > 30 kg/m2) smoking or tobacco use current pregnancy nursing mothers communication barriers

Ages Eligible for Study
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Minimum Age: 21 Years
Maximum Age: 75 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: Basic Science
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Blood Pressure Reactivity<br>Blood Pressure Responses to a cold pressor test and acute exercise will be assessed. This will be performed while subjects are on a low sodium diet (1000 mg/daily), medium sodium diet (2300 mg/daily), and high sodium diet (7000 mg/daily). | Other: Low Sodium Diet<br>* Ten days of low sodium diet<br>Other: Medium Sodium Diet<br>* Ten days of a medium sodium diet<br>Other: High Sodium Diet<br>* Ten days of a high sodium diet<br>|
| Experimental: Blood Pressure Variability<br>Twenty four hour blood pressure variability will be assessed. This will be performed while subjects are on a low sodium diet (1000 mg/daily), medium sodium diet (2300 mg/daily), and high sodium diet (7000 mg/daily). | Other: Low Sodium Diet<br>* Ten days of low sodium diet<br>Other: Medium Sodium Diet<br>* Ten days of a medium sodium diet<br>Other: High Sodium Diet<br>* Ten days of a high sodium diet<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Blood Pressure Variability | Standard deviation of systolic blood pressure over 24 hours (mmHg) | Day 10 of diet (i.e., after 10 days of low, medium, and high sodium diets; crossover design) | 
| Blood Pressure Reactivity - Handgrip exercise | Change in Blood pressure during handgrip exercise (mmHg) | Day 10 of diet (i.e., after 10 days of low, medium, and high sodium diets; crossover design) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Blood Pressure Reactivity - Cold Pressor test | Change in Blood pressure during a cold pressor test (mmHg) | Day 10 of diet (i.e., after 10 days of low, medium, and high sodium diets; crossover design) | 
| Sympathetic Responses - Handgrip exercise | Sympathetic outflow (bursts per minute) | Day 10 of diet (i.e., after 10 days of low, medium, and high sodium diets; crossover design) | 
| Sympathetic Responses - Cold Pressor test | Sympathetic outflow (bursts per minute) | Day 10 of diet (i.e., after 10 days of low, medium, and high sodium diets; crossover design) |