Neural Control of Kidney Blood Flow During Exercise in Black Adults

Overview

Black adults have a greater prevalence of developing cardiovascular and renal disease (CVRD) than white adults. Elevated sympathetic nervous system activity is associated with increased incidence of CVRD. Physical exertion, such as exercise, acutely increases sympathetic nervous system activity directed towards the kidneys, resulting in renal vasoconstriction and reduced renal blood flow (RBF). However, the acute renal vasoconstrictor response to any sympathetic nervous system activation has not been investigated to date in black adults. During sympathetic nervous system activation such as exercise, sympathetic outflow to the kidneys in black adults might be exaggerated, contributing to greater renal vasoconstriction and a larger reduction in RBF. Over time, this exaggerated neurovascular response to sympathetic activation could have a negative cumulative effect on the kidneys, which could be a contributing factor to the greater incidence of CVRD in this population. Therefore, this study aims to examine the renal vasoconstrictor response to sympathetic stressors in healthy black adults prior to development of CVRD to test the hypotheses that the renal vasoconstrictor response to acute dynamic exercise, as well as a cold pressor and mental stress tests, is exaggerated in healthy young black compared to white adults. To test these hypotheses, the investigators will measure RBF and blood pressure at rest and during cycling exercise and a cold pressor and mental stress tests to calculate renal vascular resistance responses to these acute interventions. Using the highly innovative approach of Doppler ultrasound to measure RBF during exercise and non-exercise sympathetic stressors non-invasively and with high temporal resolution will enable us to assess the renal vasoconstrictor response to sympathetic stressors in healthy black adults prior to development of CVRD, so the underlying integrative physiological responses to sympathetic activation in black adults can be understood. Findings from this study in this understudied yet clinically significant area will contribute to the ultimate goal of creating and implementing treatment strategies to reduce the risk of developing CVRD in black adults.

Full Title of Study: “Neurovascular Control of Renal Blood Flow During Exercise in Black Adults”

Study Type

  • Study Type: Interventional
  • Study Design
    • Allocation: Non-Randomized
    • Intervention Model: Parallel Assignment
    • Primary Purpose: Basic Science
    • Masking: None (Open Label)
  • Study Primary Completion Date: September 2021

Detailed Description

Black adults have a greater prevalence of developing cardiovascular and renal disease (CVRD) than white adults. Elevated sympathetic nervous system activity is associated with increased incidence of CVRD. Physical exertion, such as exercise, acutely increases sympathetic nervous system activity directed towards the kidneys, resulting in renal vasoconstriction and reduced renal blood flow (RBF). Limited research shows that healthy young black adults exhibit exaggerated sympathetic responsiveness both at rest and during sympathetic activation, which may be a major contributor to the increased risk of CVRD in this population. However, the acute renal vasoconstrictor response to any sympathetic nervous system activation has not been investigated to date in black adults. During sympathetic nervous system activation such as exercise, sympathetic outflow to the kidneys in black adults might be exaggerated, contributing to greater renal vasoconstriction and a larger reduction in RBF. Over time, this exaggerated neurovascular response to sympathetic activation could have a negative cumulative effect on the kidneys, which could be a contributing factor to the greater incidence of CVRD in this population.

Therefore, this study aims to examine the renal vasoconstrictor response to sympathetic stressors in healthy black adults prior to development of CVRD, which will be achieved via two Specific Aims. In Specific Aim 1, the investigators will test the hypothesis that the renal vasoconstrictor response to acute dynamic exercise is exaggerated in healthy young black compared to white adults. Specifically, the investigators will measure RBF and blood pressure at rest and during cycling exercise to calculate renal vascular resistance responses to exercise, enabling us to test the hypothesis that healthy young black adults exhibit an exaggerated renal vasoconstrictor response to acute cycling exercise compared to healthy young white adults. In Specific Aim 2, the investigators will test the hypothesis that the renal vasoconstrictor response to non-exercise sympathetic stressors is exaggerated in healthy young black compared to white adults. Specifically, the investigators will measure RBF and blood pressure at rest and during a cold pressor and mental stress tests to calculate renal vascular resistance responses to these non-exercise sympathetic stressors, enabling us to test the hypothesis that healthy young black adults exhibit exaggerated renal vasoconstrictor responses to non-exercise sympathetic stressors compared to healthy young white adults.

Using the highly innovative approach of Doppler ultrasound to measure RBF during exercise and non-exercise sympathetic stressors non-invasively and with high temporal resolution will enable us to assess the renal vasoconstrictor response to sympathetic stressors in healthy black adults prior to development of CVRD, so the underlying integrative physiological responses to sympathetic activation in black adults can be understood. Findings from this study in this understudied yet clinically significant area will contribute to the ultimate goal of creating and implementing treatment strategies to reduce the risk of developing CVRD in black adults.

Interventions

  • Other: Acute exercise
    • Participants will lie in a supine position with their feet attached to the pedals of a custom-arranged cycle ergometer. Participants’ 40% heart rate reserve will be calculated, giving the target value to achieve during exercise based on appropriate resistance applied on the cycle ergometer, corresponding to a mild-to-moderate exercise intensity. After a 5-minute resting baseline, participants will perform dynamic cycling exercise for up to 20 minutes. They will then stop exercising, and there will be a 5-minute recovery period. Beat-to-beat renal blood flow velocity (Doppler ultrasound), mean arterial blood pressure (finger photoplethysmographic cuff), and heart rate (electrocardiogram) will be recorded throughout. A rating of perceived exertion will be taken from participants during the last 30 seconds of steady-state cycling exercise.
  • Other: Cold pressor test
    • Participants will lie in a supine position, and after a 3-minute resting baseline, participants will have their hand immersed in ice water for 2 minutes. This cold pressor test represents the non-exercise, physical sympathetic stressor. Participants’ hand will then be removed from the ice water, followed by a 3-minute recovery period. Beat-to-beat renal blood flow velocity (Doppler ultrasound), mean arterial blood pressure (finger photoplethysmographic cuff), and heart rate (electrocardiogram) will be recorded throughout. Ratings of hand pain and cold perception will be taken from participants during the last 30 seconds of the cold pressor test.
  • Other: Mental stress test
    • Participants will lie in a supine position, and after a 3-minute resting baseline, participants will perform a mental arithmetic task for 5 minutes. This mental stress test represents the non-exercise, psychological sympathetic stressor. Participants will be instructed to subtract a given number from a randomly selected three-digit number and verbally state their answer and continue to do so for the duration of the test. Participants will then stop the arithmetic task, and a 3-minute recovery period will follow. Beat-to-beat renal blood flow velocity (Doppler ultrasound), mean arterial blood pressure (finger photoplethysmographic cuff), and heart rate (electrocardiogram) will be recorded throughout. A rating of perceived stress will be taken from participants during the last 30 seconds of the mental stress test.

Arms, Groups and Cohorts

  • Experimental: Black Adults
    • Black adults will undergo the interventions of acute exercise, a cold pressor test, and a mental stress test while beat-to-beat renal blood flow velocity, mean arterial blood pressure, and heart rate are recorded.
  • Experimental: White Adults
    • White adults will undergo the interventions of acute exercise, a cold pressor test, and a mental stress test while beat-to-beat renal blood flow velocity, mean arterial blood pressure, and heart rate are recorded.

Clinical Trial Outcome Measures

Primary Measures

  • Change in renal vascular resistance during acute exercise
    • Time Frame: Pre-acute exercise and during steady-state exercise
    • For the acute exercise intervention, the percent change from pre-acute exercise to during steady-state exercise will be assessed.
  • Change in renal vascular resistance during cold pressor test
    • Time Frame: Pre-cold pressor test to after 30, 60, 90, and 120 seconds of cold pressor test
    • For the cold pressor test intervention, the percent change from pre-cold pressor test to 30-second intervals during the cold pressor test will be assessed.
  • Change in renal vascular resistance during mental stress test
    • Time Frame: Pre-mental stress test to after 1, 2, 3, 4, and 5 minutes of mental stress test
    • For the mental stress test intervention, the percent change from pre-mental stress test to 1-minute intervals during the mental stress test will be assessed.

Secondary Measures

  • Change in renal blood flow velocity during acute exercise
    • Time Frame: Pre-acute exercise and during steady-state exercise
    • For the acute exercise intervention, the absolute change from pre-acute exercise to during steady-state exercise will be assessed.
  • Change in mean arterial blood pressure during acute exercise
    • Time Frame: Pre-acute exercise and during steady-state exercise
    • For the acute exercise intervention, the absolute change from pre-acute exercise to during steady-state exercise will be assessed.
  • Change in systolic blood pressure during acute exercise
    • Time Frame: Pre-acute exercise and during steady-state exercise
    • For the acute exercise intervention, the absolute change from pre-acute exercise to during steady-state exercise will be assessed.
  • Change in diastolic blood pressure during acute exercise
    • Time Frame: Pre-acute exercise and during steady-state exercise
    • For the acute exercise intervention, the absolute change from pre-acute exercise to during steady-state exercise will be assessed.
  • Change in heart rate during acute exercise
    • Time Frame: Pre-acute exercise and during steady-state exercise
    • For the acute exercise intervention, the absolute change from pre-acute exercise to during steady-state exercise will be assessed.
  • Change in cardiac output during acute exercise
    • Time Frame: Pre-acute exercise and during steady-state exercise
    • For the acute exercise intervention, the absolute change from pre-acute exercise to during steady-state exercise will be assessed.
  • Change in stroke volume during acute exercise
    • Time Frame: Pre-acute exercise and during steady-state exercise
    • For the acute exercise intervention, the absolute change from pre-acute exercise to during steady-state exercise will be assessed.
  • Change in total peripheral resistance during acute exercise
    • Time Frame: Pre-acute exercise and during steady-state exercise
    • For the acute exercise intervention, the absolute change from pre-acute exercise to during steady-state exercise will be assessed.
  • Change in renal blood flow velocity during cold pressor test
    • Time Frame: Pre-cold pressor test to after 30, 60, 90, and 120 seconds of cold pressor test
    • For the cold pressor test intervention, the absolute change from pre-cold pressor test to 30-second intervals during the cold pressor test will be assessed.
  • Change in mean arterial blood pressure during cold pressor test
    • Time Frame: Pre-cold pressor test to after 30, 60, 90, and 120 seconds of cold pressor test
    • For the cold pressor test intervention, the absolute change from pre-cold pressor test to 30-second intervals during the cold pressor test will be assessed.
  • Change in systolic blood pressure during cold pressor test
    • Time Frame: Pre-cold pressor test to after 30, 60, 90, and 120 seconds of cold pressor test
    • For the cold pressor test intervention, the absolute change from pre-cold pressor test to 30-second intervals during the cold pressor test will be assessed.
  • Change in diastolic blood pressure during cold pressor test
    • Time Frame: Pre-cold pressor test to after 30, 60, 90, and 120 seconds of cold pressor test
    • For the cold pressor test intervention, the absolute change from pre-cold pressor test to 30-second intervals during the cold pressor test will be assessed.
  • Change in heart rate during cold pressor test
    • Time Frame: Pre-cold pressor test to after 30, 60, 90, and 120 seconds of cold pressor test
    • For the cold pressor test intervention, the absolute change from pre-cold pressor test to 30-second intervals during the cold pressor test will be assessed.
  • Change in cardiac output during cold pressor test
    • Time Frame: Pre-cold pressor test to after 30, 60, 90, and 120 seconds of cold pressor test
    • For the cold pressor test intervention, the absolute change from pre-cold pressor test to 30-second intervals during the cold pressor test will be assessed.
  • Change in stroke volume during cold pressor test
    • Time Frame: Pre-cold pressor test to after 30, 60, 90, and 120 seconds of cold pressor test
    • For the cold pressor test intervention, the absolute change from pre-cold pressor test to 30-second intervals during the cold pressor test will be assessed.
  • Change in total peripheral resistance during cold pressor test
    • Time Frame: Pre-cold pressor test to after 30, 60, 90, and 120 seconds of cold pressor test
    • For the cold pressor test intervention, the absolute change from pre-cold pressor test to 30-second intervals during the cold pressor test will be assessed.
  • Change in renal blood flow velocity during mental stress test
    • Time Frame: Pre-mental stress test to after 1, 2, 3, 4, and 5 minutes of mental stress test
    • For the mental stress test intervention, the absolute change from pre-mental stress test to 1-minute intervals during the mental stress test will be assessed.
  • Change in mean arterial blood pressure during mental stress test
    • Time Frame: Pre-mental stress test to after 1, 2, 3, 4, and 5 minutes of mental stress test
    • For the mental stress test intervention, the absolute change from pre-mental stress test to 1-minute intervals during the mental stress test will be assessed.
  • Change in systolic blood pressure during mental stress test
    • Time Frame: Pre-mental stress test to after 1, 2, 3, 4, and 5 minutes of mental stress test
    • For the mental stress test intervention, the absolute change from pre-mental stress test to 1-minute intervals during the mental stress test will be assessed.
  • Change in diastolic blood pressure during mental stress test
    • Time Frame: Pre-mental stress test to after 1, 2, 3, 4, and 5 minutes of mental stress test
    • For the mental stress test intervention, the absolute change from pre-mental stress test to 1-minute intervals during the mental stress test will be assessed.
  • Change in heart rate during mental stress test
    • Time Frame: Pre-mental stress test to after 1, 2, 3, 4, and 5 minutes of mental stress test
    • For the mental stress test intervention, the absolute change from pre-mental stress test to 1-minute intervals during the mental stress test will be assessed.
  • Change in cardiac output during mental stress test
    • Time Frame: Pre-mental stress test to after 1, 2, 3, 4, and 5 minutes of mental stress test
    • For the mental stress test intervention, the absolute change from pre-mental stress test to 1-minute intervals during the mental stress test will be assessed.
  • Change in stroke volume during mental stress test
    • Time Frame: Pre-mental stress test to after 1, 2, 3, 4, and 5 minutes of mental stress test
    • For the mental stress test intervention, the absolute change from pre-mental stress test to 1-minute intervals during the mental stress test will be assessed.
  • Change in total peripheral resistance during mental stress test
    • Time Frame: Pre-mental stress test to after 1, 2, 3, 4, and 5 minutes of mental stress test
    • For the mental stress test intervention, the absolute change from pre-mental stress test to 1-minute intervals during the mental stress test will be assessed.

Participating in This Clinical Trial

Inclusion Criteria

  • Self-report identify as either black or white racial identity
  • Born in United States
  • Both parents identify as same racial identity as participant
  • Fluent in English

Exclusion Criteria

  • Pregnancy
  • Cardiovascular or renal disease
  • Hypertension (blood pressure of more than or equal to 130/80 mmHg)
  • Diabetes
  • Obese (body mass index of more than or equal to 30 kg/m2)
  • Smoker/Tobacco use
  • Athletically trained
  • Taking prescribed medications with exception of birth control pills

Gender Eligibility: All

Minimum Age: 18 Years

Maximum Age: 35 Years

Are Healthy Volunteers Accepted: Accepts Healthy Volunteers

Investigator Details

  • Lead Sponsor
    • University of Massachusetts, Boston
  • Provider of Information About this Clinical Study
    • Principal Investigator: Rachel Drew, Assistant Professor – University of Massachusetts, Boston
  • Overall Official(s)
    • Rachel C Drew, PhD, Principal Investigator, University of Massachusetts, Boston
  • Overall Contact(s)
    • Rachel C Drew, PhD, (617) 287-4061, rachel.drew@umb.edu

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