# Exercise Pressor Reflex Dysfunction in Heart Failure: Mechanisms and Treatment

> **NIH NIH R01** · KANSAS STATE UNIVERSITY · 2021 · $298,410

## Abstract

PROJECT SUMMARY
 There are currently ~6.5 million men and women in the United States with heart failure. By 2030, that
number is predicted to climb to over 8.5 million and direct heart failure-related health care costs are predicted to
command $53.1 billion. Heart failure patients commonly exhibit exaggerated levels of sympathetic nervous
system activity at rest and during exercise compared to healthy subjects. An exaggerated increase in
sympathetic nervous system activity during exercise (i.e., sympatho-excitation) is a direct contributor to exercise
intolerance and lack of functional independence which is the main reason that heart failure patients seek medical
care. A neural reflex that is activated by mechanical and metabolic signals within contracting skeletal muscles
contributes importantly to the increase in sympathetic nervous system activity that occurs during exercise. In
heart failure patients, the activation of this reflex, termed the exercise pressor reflex, is exaggerated which
underlies mechanistically the exercise-induced sympatho-excitation. Currently, there are no therapies that are
designed specifically to reduce the activation of the exercise pressor reflex in heart failure patients which reflects
our current limited understanding of the mechanisms that contribute to its exaggeration. We will use male and
female rats with surgically-induced heart failure (post-myocardial infarction model) to study the mechanistic
bases and possible therapeutic targets of the exaggerated exercise pressor reflex. In Aim 1, we will investigate
the role played by endoperoxide (EP) 4 receptors, which are stimulated by prostaglandins produced within
skeletal muscles, in evoking the exercise pressor reflex in heart failure. In Aim 2, we will investigate the role
played by mechanically activated piezo2 channels in evoking the exercise pressor reflex in heart failure. In Aim
3, we will investigate whether peripheral δ-opioid receptor stimulation reduces the exercise pressor reflex in heart
failure. We will investigate these aims using a complementary blend of whole animal and molecular level
approaches so that our findings are integrative and translational. Collectively, our experiments may identity three
possible targets (EP4 receptors, piezo2 channels, and δ-opioid receptors) for therapies aimed at 1) mitigating
the sympatho-excitation that occurs during exercise and 2) increasing exercise tolerance, functional
independence, and overall quality of life in heart failure patients.

## Key facts

- **NIH application ID:** 10222760
- **Project number:** 5R01HL142877-04
- **Recipient organization:** KANSAS STATE UNIVERSITY
- **Principal Investigator:** Steven W Copp
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $298,410
- **Award type:** 5
- **Project period:** 2018-08-01 → 2023-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10222760

## Citation

> US National Institutes of Health, RePORTER application 10222760, Exercise Pressor Reflex Dysfunction in Heart Failure: Mechanisms and Treatment (5R01HL142877-04). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10222760. Licensed CC0.

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