Neural Control of Kidney Blood Flow During Exercise in African American Adults

Study Overview
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Brief Summary
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African American (AA) adults have a greater prevalence of developing cardiovascular and renal disease (CVRD) than White (W) 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 AA adults. During sympathetic nervous system activation such as exercise, sympathetic outflow to the kidneys in AA 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 AA 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 AA compared to W 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 AA adults prior to development of CVRD, so the underlying integrative physiological responses to sympathetic activation in AA 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 AA adults.

Detailed Description
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African American (AA) adults have a greater prevalence of developing cardiovascular and renal disease (CVRD) than White (W) 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 AA 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 AA adults. During sympathetic nervous system activation such as exercise, sympathetic outflow to the kidneys in AA 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 AA 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 AA compared to W 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 AA adults exhibit an exaggerated renal vasoconstrictor response to acute cycling exercise compared to healthy young W 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 AA compared to W 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 AA adults exhibit exaggerated renal vasoconstrictor responses to non-exercise sympathetic stressors compared to healthy young W 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 AA adults prior to development of CVRD, so the underlying integrative physiological responses to sympathetic activation in AA 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 AA adults.

Official Title
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Neurovascular Control of Renal Blood Flow During Exercise in African American Adults

Conditions
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Acute Exercise

Intervention / Treatment
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* Other: Acute exercise
* Other: Cold pressor test
* Other: Mental stress test


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Self-report as either African American or White racial identity Born in United States Both biological parents identify as same racial identity as participant Recreationally active (participating in physical activity for at least 20 minutes per day, at least three times per week, but not training for competitive events) Fluent in English Exclusion Criteria: Hispanic or Latino Females who are pregnant or lactating Cardiovascular or renal disease Hypertension (blood pressure of more than or equal to 130/80 mmHg) Diabetes Obesity (body mass index of more than or equal to 30 kg/m2) Smoker/Tobacco user Acute medical conditions Taking prescribed medications with exception of birth control pills

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 35 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: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: African American Adults<br>African American 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. | Other: Acute exercise<br>* Participants will lie in a semi-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 moderate exercise intensity. After a 5-minute resting baseline, participants will perform dynamic cycling exercise at steady state 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.<br>Other: Cold pressor test<br>* Participants will lie in a semi-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.<br>Other: Mental stress test<br>* Participants will lie in a semi-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 be instructed to state their answers as quickly and accurately as possible. 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.<br>|
| Experimental: White Adults<br>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. | Other: Acute exercise<br>* Participants will lie in a semi-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 moderate exercise intensity. After a 5-minute resting baseline, participants will perform dynamic cycling exercise at steady state 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.<br>Other: Cold pressor test<br>* Participants will lie in a semi-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.<br>Other: Mental stress test<br>* Participants will lie in a semi-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 be instructed to state their answers as quickly and accurately as possible. 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.<br>|

What is the study measuring?
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Primary Outcome Measures

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

Secondary Outcome Measures

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

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Exercise, Cold stress, Mental stress