Adverse Neurogenic Actions of Dietary Salt

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.

Study Overview

• Status: Completed
• Conditions: Blood Pressure
• Intervention / Treatment: Other: Low Sodium Diet; Other: Medium Sodium Diet; Other: High Sodium Diet

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 77
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: William B Farquhar, PhD; Phone Number: 302-831-6178; Email: wbf@udel.edu
• Study Contact Backup: Name: Megan Wenner, PhD; Phone Number: 302-831-7343; Email: mwenner@udel.edu

Study Locations

• United States
  • Delaware
    • Newark, Delaware, United States, 19716
      • University of Delaware

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 21 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Blood Pressure Reactivity; 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; Ten days of low sodium diet; Other: Medium Sodium Diet; Ten days of a medium sodium diet; Other: High Sodium Diet; Ten days of a high sodium diet
Experimental: Blood Pressure Variability; 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; Ten days of low sodium diet; Other: Medium Sodium Diet; Ten days of a medium sodium diet; Other: High Sodium Diet; Ten days of a high sodium diet

What is the study measuring?

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)

Collaborators and Investigators

• Sponsor: University of Delaware
• Investigators: Principal Investigator: William B Farquhar, PhD, University of Delaware

Publications and helpful links

General Publications

• Migdal KU, Babcock MC, Robinson AT, Watso JC, Wenner MM, Stocker SD, Farquhar WB. The Impact of High Dietary Sodium Consumption on Blood Pressure Variability in Healthy, Young Adults. Am J Hypertens. 2020 Apr 29;33(5):422-429. doi: 10.1093/ajh/hpaa014.

Study record dates

Study Major Dates

• Study Start (Actual): April 1, 2016
• Primary Completion (Actual): November 22, 2022
• Study Completion (Actual): November 22, 2022

Study Registration Dates

• First Submitted: August 15, 2016
• First Submitted That Met QC Criteria: August 23, 2016
• First Posted (Estimate): August 29, 2016

Study Record Updates

• Last Update Posted (Actual): March 23, 2023
• Last Update Submitted That Met QC Criteria: March 22, 2023
• Last Verified: March 1, 2023

More Information

Terms related to this study

• Other Study ID Numbers: 819183

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED