# Neurovascular Regulation During Exercise In Humans With Chronic Kidney Disease

> **NIH NIH R01** · EMORY UNIVERSITY · 2021 · $390,000

## Abstract

Project Summary/Abstract
Chronic kidney disease (CKD) patients are at significantly higher risk of cardiovascular (CV) mortality. One
prominent feature of CKD that is independently associated with increased CV risk is exercise intolerance. Our
prior studies show that CKD patients have an exaggerated increase in blood pressure (BP) during both
moderate and low-intensity exercise. Such exaggerated BP responses could contribute to an increased risk of
CV events not only during exercise, but also during day to day activities, and represent a new and unexplored
mechanistic link between exercise intolerance and CV risk in CKD. Our long-term goals are to elucidate the
mechanisms underlying abnormal hemodynamic responses during physical activity in CKD, which can inform
development of therapies that target these underlying aberrancies, improve hemodynamics both at rest and
during physical activity, and ultimately improve CV outcomes. We previously showed that the degree of
increase in BP for the same degree of increase in sympathetic nerve activity (SNA) during exercise is
significantly higher in CKD patients compared to Controls. These findings suggest that CKD patients have an
augmented vasoconstrictive response, i.e. greater neurovascular transduction, in response to exercise-induced
SNS activation, leading to an augmented exercise pressor response. Aim 1 seeks to elucidate the
mechanisms that differentially modulate neurovascular transduction of SNA in CKD. Specifically, we will test
the hypothesis that CKD patients have an impaired capacity to oppose SNS-mediated vasoconstriction within
exercising skeletal muscle, defined as functional sympatholysis, which is associated with enhanced
neurovascular transduction of SNA during exercise. We will also test the hypothesis that CKD patients have
heightened vascular α1-adrenergic receptor (AR) sensitivity, leading to a greater degree of vasoconstriction in
response to exercise-induced SNS activation. To translate these studies into the clinical arena, in Aim 2, we
will conduct a clinical trial testing the potential benefits of a multifaceted intervention targeting the underlying
derangements of impaired functional sympatholysis and heightened vascular α1-AR sensitivity. Since both
functional sympatholysis and vascular α1-AR sensitivity are modulated by nitric oxide (NO), and CKD patients
have decreased NO bioavailability, we will determine if strategies to improve NO bioavailability
nonpharmacologically (via aerobic exercise training), and pharmacologically (via tetrahydrobiopterin (BH4)
supplementation) improves hemodynamic and neurovascular responses during exercise in CKD. Using a 2x2
factorial design randomized controlled trial, we will test the hypothesis that exercise training and BH4
supplementation independently and synergistically improve the primary outcomes of exaggerated exercise
pressor responses, impaired functional sympatholysis, and heightened vascular α1-AR sensitivity in CKD.
These studies...

## Key facts

- **NIH application ID:** 10085668
- **Project number:** 5R01HL135183-05
- **Recipient organization:** EMORY UNIVERSITY
- **Principal Investigator:** Jeanie Park
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $390,000
- **Award type:** 5
- **Project period:** 2017-01-01 → 2022-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10085668

## Citation

> US National Institutes of Health, RePORTER application 10085668, Neurovascular Regulation During Exercise In Humans With Chronic Kidney Disease (5R01HL135183-05). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10085668. Licensed CC0.

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