Racial Differences in Serum Sodium and Blood Pressure Regulation

Nearly nine-in-ten Americans overconsume salt. Black individuals are more prone to salt-sensitive hypertension. The central goal of the study is to determine if dietary sodium influences blood vessel function and nervous system regulation of blood pressure differentially in black, compared to white individuals. These findings may help to explain why high dietary salt causes increases in blood pressure more frequently in black, compared to white individuals. A secondary goal of this project is to also determine the role of lifestyle factors (i.e., sleep, physical activity, and nutrition) on potential baseline racial differences in cardiovascular function.

Study Overview

• Status: Recruiting
• Conditions: Blood Pressure; Cardiovascular Risk Factor; Sodium Excess; Racial Disparities
• Intervention / Treatment: Other: Acute Salt (sodium chloride)

Detailed Description

The investigators aim to study racial differences in cardiovascular responses to high dietary sodium. An overwhelming majority of Americans consume more dietary sodium than what is recommended by the American Heart Association and the Dietary Guidelines for Americans. The investigators recently published data demonstrating that compared to white individuals, 1) black individuals have augmented increases in serum sodium concentration to a hypertonic saline infusion; and 2) exhibit higher blood pressure for a given serum sodium. In this proposal, the investigators will translate these findings by comprehensively assessing neurovascular responses to acute (single meal) high dietary sodium. The central hypothesis is that high dietary sodium influences sympathetic nerve activity similarly in black and white individuals; however, diminished vasodilator capacity and augmented sympathetic transduction (vasoconstrictor responses to sympathetic nerve bursts) contribute to exaggerated blood pressure dysregulation in black individuals. The investigators will also determine the role of lifestyle factors (i.e., sleep, physical activity, and nutrition) on potential baseline racial differences in cardiovascular function.

• Study Type: Interventional
• Enrollment (Estimated): 100
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Rodney Greer, PhD; Phone Number: (334) 844-3597; Email: rjg0008@auburn.edu

Study Locations

• United States
  • Alabama
    • Auburn, Alabama, United States, 36849
      • Recruiting
      • Auburn University
      • Contact: Austin T Robinson, PhD; Phone Number: 574-514-1034; Email: atr0026@auburn.edu
      • Contact: Zachary J Hutchison, MS; Phone Number: 3348441619; Email: zzh0026@auburn.edu
      • Principal Investigator: Austin T Robinson, PhD
    • Auburn, Alabama, United States, 36849
      • Recruiting
      • Kinesiology Building
      • Contact: Mary Rudisill, PhD; Phone Number: 334-844-1458; Email: rudisme@auburn.edu
      • Contact: Jared Russell, PhD; Phone Number: (334) 844-1429; Email: russej3@auburn.edu
      • Principal Investigator: Austin Robinson, PhD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 19 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

1. Are between the ages of 19-75.
2. Have blood pressure no higher than 150/90 mmHg.
3. Have a BMI below 35 Kg/m2 (otherwise healthy)
4. Free from metabolic disease (diabetes or renal disease), pulmonary disorders (e.g., COPD & cystic fibrosis), and cardiovascular disease (peripheral vascular, cardiac, or cerebrovascular).
5. Do not have any precluding medical issues that prevent participants from exercising (i.e., cardiovascular issues, or muscle/joint issues including painful arthritis) or giving blood (e.g., blood thinners).
6. Are not currently smoking, using smokeless tobacco, nor smoked within the past 12 months.

Exclusion Criteria:

1. High blood pressure - greater the 150/90 mmHg
2. Low blood pressure - less than 90/50 mmHg
3. History of cardiovascular disease
4. History of cancer
5. History of diabetes
6. History of kidney disease
7. Obesity (BMI > 30 kg/m2)
8. Smoking or tobacco use
9. Current pregnancy
10. Nursing mothers
11. Communication barriers

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: High Sodium Meal (2500 mg sodium); Participants will have sympathetic nerve activity, vascular function, blood pressure and blood samples (from intravenous catheters) assessed before and after a high sodium meal (2500 mg sodium).	Other: Acute Salt (sodium chloride); Varied amounts of salt (sodium chloride) will be added to a very low sodium soup to determine the effects of a single high sodium meal on measures of vascular function and autonomic regulation of blood pressure
Placebo Comparator: Low Sodium Meal (140 mg sodium); Participants will have sympathetic nerve activity, vascular function, blood pressure and blood samples (from intravenous catheters) assessed before and after a low sodium meal (140 mg sodium) which will serve as the control condition to demonstrate whether or not observed changes are due to high sodium or occur irrespective of sodium in the postprandial state.	Other: Acute Salt (sodium chloride); Varied amounts of salt (sodium chloride) will be added to a very low sodium soup to determine the effects of a single high sodium meal on measures of vascular function and autonomic regulation of blood pressure

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Changes in muscle sympathetic nerve activity (MSNA) and sympathetic transduction	The investigators will directly record MSNA using an active tungsten microelectrode inserted into a nerve near the fibular head or popliteal fossa using standard microneurography techniques. The raw signal will be amplified, band-pass filtered, rectified, and integrated using a nerve traffic analyzer. The presence of MSNA will be confirmed by a pulse-synchronous signal that responds to an end-expiratory breath-hold and stimulation of muscle (tendon tapping), but not skin afferents (gentle skin stroke and/or startle stimulus). MSNA will be expressed as bursts per minute and per 100 cardiac cycles. Further, the investigators will measure common femoral artery blood flow using ultrasound and mean arterial pressure using photoplethysmography. This will allow determination of sympathetic transduction (the vasoconstrictor and pressor effects of MSNA) expressed as changes in blood pressure (mmHg) or changes in vascular conductance (ml blood flow/mmHg).	Before and one hour after soup, both conditions (high- and low-salt)
Changes in flow-mediated dilation (FMD)	Flow-mediated vasodilation will be assessed using continuous measures of brachial artery diameter and velocity via duplex Doppler ultrasound (Hitachi Arietta 70). The brachial artery will be imaged in the longitudinal plane proximal to the medial epicondyle using a high-frequency (6-12 MHz) linear-array probe. The ultrasound probe will be stabilized using a custom-built clamp. Shear rate (sec-1) will be calculated as [(blood flow velocity (cm*s-1) *4)/blood vessel diameter (mm)] The image will be recorded throughout a 60-s baseline, a 300-s ischemic stimulus (250 mmHg), and 180 seconds post deflation. FMD will be expressed as % dilation (final diameter-baseline diameter/baseline diameter x 100) and also normalized to the shear stimulus. Allometric scaling will be used if appropriate, including if there are baseline differences in artery diameter by race or condition.	Before, 30 minutes, and one hour after soup, both conditions (high- and low- salt)
Changes in indices of arterial stiffness	The investigators will use the SphygmoCor XCEL system to assess pulse wave analysis (PWA) and pulse wave velocity (PWV). A high-fidelity strain-gauge transducer is used to obtain the pressure waveform at the carotid and radial pulse. Distances from the carotid artery sampling site to the femoral artery (upper leg instrumented with a thigh cuff for oscillometric sphygmomanometry), and from the carotid artery to the suprasternal notch will be recorded. The investigators will also assess forward and reflective wave magnitudes. PWV will be expressed as cm/s and PWA will be expressed as % (calculated as augmentation pressure divided by the pulse pressure).	Before 30 minutes, and one hour after soup, both conditions (high- and low- salt)
Changes in blood pressure reactivity	The investigators will measure systolic and diastolic pressure using photoplethysmography at the finger. Systolic and diastolic blood pressure will be assessed at rest and during handgrip exercise. Blood pressure reactivity will be expressed as a change in pressure (mmHg) from baseline to a predetermined time during the stressor (e.g., minute one average and minute two average).	Before and one hour after soup, both conditions (high- and low- salt)
Changes in blood biomarkers of nitric oxide bioavailability	The investigators will measure nitric oxide metabolites (nitrate and nitrite nanomolar concentration).	Before, 30 minutes, and one hour after soup, both conditions (high- and low- salt)
Changes in circulating reactive oxygen species	We will use electron paramagnetic resonance to measure reactive oxygen species (spectra units) in whole blood samples treated with a spin probe.	Before, 30 minutes, and one hour after soup, both conditions (high- and low- salt)
Changes in circulating inflammatory cytokines	We will measure inflammatory markers (nano- or picograms per deciliter) via enzym linked immunoabsorbent assays.	Before, 30 minutes, and one hour after soup, both conditions (high- and low- salt)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Objective sleep duration and quality	Philips actiwatch spectrum will be used to quantify sleep duration. Participants will wear the watch units for 7 days. We will assess qualitative sleep scores and cross-check actigraphy wear times with a sleep diary.	Baseline (pre-intervention)
Subjective Sleep duration and quality	We will use the Pittsburgh Sleep Quality Index to asses sleep duration and perceived sleep quality reflective of the one month period leading into the study.	Baseline (pre-intervention)
Physical activity	Participants will wear an ActiGraph GT3X accelerometer for seven days to objectively quantify steps per day and metabolic equivalents per day.	Baseline (pre-intervention)
Cardio-respiratory fitness	We will use indirect calorimetry to measure the participant's maximal oxygen consumption (VO2max) during incremental exercise on a treadmill. We will use a Parvo TrueOne metabolic cart and Woodway treadmill.	Baseline (pre-intervention)
Mental health - social anxiety	We will administer the Liebowitz Social Anxiety Scale. The scale starts at 0 (none) and ends at 3 (severe) for 24 questions related to anxiety and avoidance, and a cumulative score is calculated.	Baseline (pre-intervention)
Mental health - depression	We will administer the Beck's Depression Inventory. The scale starts at 0 and ends at 3 for 21 questions related to depression.	Baseline (pre-intervention)
Habitual dietary intake	We will instruct participants to complete a diet log for 6 days which will be operationalized with Nutrition Data System for Research (NDSR).	Baseline (pre-intervention)

Collaborators and Investigators

• Sponsor: Auburn University
• Collaborators: University of Delaware
• Investigators: Principal Investigator: Austin T Robinson, PhD, Auburn University

Publications and helpful links

General Publications

• Wenner MM, Paul EP, Robinson AT, Rose WC, Farquhar WB. Acute NaCl Loading Reveals a Higher Blood Pressure for a Given Serum Sodium Level in African American Compared to Caucasian Adults. Front Physiol. 2018 Oct 1;9:1354. doi: 10.3389/fphys.2018.01354. eCollection 2018.
• Babcock MC, Robinson AT, Migdal KU, Watso JC, Wenner MM, Stocker SD, Farquhar WB. Reducing Dietary Sodium to 1000 mg per Day Reduces Neurovascular Transduction Without Stimulating Sympathetic Outflow. Hypertension. 2019 Mar;73(3):587-593. doi: 10.1161/HYPERTENSIONAHA.118.12074.
• Dickinson KM, Clifton PM, Burrell LM, Barrett PH, Keogh JB. Postprandial effects of a high salt meal on serum sodium, arterial stiffness, markers of nitric oxide production and markers of endothelial function. Atherosclerosis. 2014 Jan;232(1):211-6. doi: 10.1016/j.atherosclerosis.2013.10.032. Epub 2013 Nov 20.
• Migdal KU, Robinson AT, Watso JC, Babcock MC, Serrador JM, Farquhar WB. A high-salt meal does not augment blood pressure responses during maximal exercise. Appl Physiol Nutr Metab. 2020 Feb;45(2):123-128. doi: 10.1139/apnm-2019-0217. Epub 2019 Jun 25.

Helpful Links

• PI's laboratory

Study record dates

Study Major Dates

• Study Start (Actual): May 3, 2021
• Primary Completion (Estimated): August 31, 2024
• Study Completion (Estimated): May 31, 2025

Study Registration Dates

• First Submitted: December 5, 2019
• First Submitted That Met QC Criteria: January 24, 2020
• First Posted (Actual): January 28, 2020

Study Record Updates

• Last Update Posted (Actual): August 15, 2023
• Last Update Submitted That Met QC Criteria: August 14, 2023
• Last Verified: August 1, 2023

More Information

Terms related to this study

• Keywords: sleep; blood pressure; diet; cardiovascular health; physical fitness; racial disparities; dietary sodium; dietary salt
• Additional Relevant MeSH Terms: Metabolic Diseases; Water-Electrolyte Imbalance; Hypernatremia
• Other Study ID Numbers: AU IRB#19-390

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Data with all HIPAA identifiers removed may be shared in future collaborative efforts pending appropriate DMDA approvals
• IPD Sharing Time Frame: One year after completion of trial, indefinitely
• IPD Sharing Access Criteria: A formal plan identifying the intended use fo the data and proper completion of a DMDA and MTA (if needed) with Auburn University and the study PI.
• IPD Sharing Supporting Information Type: SAP; ICF; ANALYTIC_CODE

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No