Dietary Sodium, Oxidative Stress, and Pulsatile Hemodynamics

Study Overview
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Brief Summary
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High sodium diets impair vascular function, which may influence the work of the heart. This investigation is designed to determine if this change in vascular function results in a greater workload in the heart and if people who regularly exercise are protected from these effects.

Detailed Description
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Excess dietary sodium is associated with cardiac hypertrophy independent of changes in blood pressure. Importantly, increased arterial pulsatile load predicts left ventricular hypertrophy, and thus presents a potential mechanism through which high dietary sodium augments cardiovascular disease risk. While high sodium diets impair vascular function via an increase in oxidative stress, how high sodium influences central pulsatile hemodynamics is not known. This project aims to a) determine how impaired vascular function affects pulsatile hemodynamics and thus influences the work of the heart during periods of high sodium consumption and b) examine whether regular aerobic exercise and/or fitness protects against the deleterious effects of excess sodium.

Official Title
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The Role of Oxidative Stress and Endothelial Dysfunction in High Sodium-Induced Changes in Pulsatile Hemodynamics

Conditions
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Sodium Excess

Intervention / Treatment
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* Dietary Supplement: High Sodium
* Other: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Healthy individuals (age 21-45) who are either sedentary (1 or less days of exercise per week during past year) or habitually active (4 or more days of aerobic exercise per week for a minimum of 1 year) Exclusion Criteria: Body mass index <18 or >35 Systolic blood pressure ≥140 mmHg and/or diastolic blood pressure ≥90 Blood donation within past 8 weeks, Glucose 6 phosphate dehydrogenase (G6PD) deficiency A history of cancer, diabetes, or any other chronic disease A history of any heart disease A history of hormone therapy Use of nicotine products Pregnancy Nursing mothers Participation in regular physical activity greater than 1 day/week- but less than 4 days/week

Ages Eligible for Study
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Minimum Age: 21 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: Prevention
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: High Sodium<br>Consumption of an extra 3900 mg of dietary sodium per day. | Dietary Supplement: High Sodium<br>* 10 days of 3900 mg of sodium/day in excess of normal dietary intake delivered via enteric capsules filled with table salt.<br>|
| Placebo Comparator: Placebo<br>Control Condition | Other: Placebo<br>* 10 days of enteric capsules filled with dextrose.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Reflected Pulse Wave Amplitude | Aortic pressure-flow relations will be assessed non-invasively using echocardiography and peripheral artery applanation tonometry. Wave separation analysis will be used to calculate reflected pulse wave amplitude. | On the 10th day of each arm. | 
| Conduit artery endothelium-dependent dilation | Brachial artery flow mediated dilation (FMD) will be assessed by duplex ultrasound as an index of conduit artery endothelial function. | On the 10th day of each arm. | 
| Arterial Stiffness | Carotid-femoral pulse wave velocity (cf-PWV) will be assessed via applanation tonometry as an index of aortic stiffness. cf-PWV will be calculated as the difference in timing of of pulse waves at the carotid and femoral arteries divided by the distance between measurements. | On the 10th day of each arm. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Wave reflection timing | Aortic pressure-flow relations will be assessed non-invasively using echocardiography and peripheral artery applanation tonometry. Wave separation analysis will be used to calculate reflected wave transit time. | On the 10th day of each arm. | 
| Forward Pulse Wave Amplitude | Aortic pressure-flow relations will be assessed non-invasively using echocardiography and peripheral artery applanation tonometry. Wave separation analysis will be used to the amplitude of the forward traveling pulse wave. | On the 10th day of each arm. | 
| 24 Hour Blood Pressure | 24 hour blood pressure monitoring will be performed using an ambulatory blood pressure monitor device. Average day and nighttime systolic, diastolic, and mean blood pressures will be determined. | The morning of day 9 through the morning of day 10 for each arm. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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endothelium, oxidative stress, physical activity, ventricular-vascular coupling, pulsatile load