# Role of Sensory Neurons in Human Cardiovascular Disease

> **NIH NIH R01** · UTAH STATE HIGHER EDUCATION SYSTEM--UNIVERSITY OF UTAH · 2020 · $381,250

## Abstract

ABSTRACT
 Patients with hypertension (HTN) are characterized by an exaggerated blood pressure response and
premature fatigue during physical activities. An abnormal exercise pressor reflex (EPR) mediated by neural
feedback from mechano- and/or metabosensitive group III and IV muscle afferents might contribute to these
abnormalities. However, even in health, our understanding of the exact role and relative contribution of group
III/IV afferents to the circulatory control and the development of fatigue during exercise is incomplete. By studying
both HTN patients and well-matched healthy controls (CTRLs), we will evaluate the impact of HTN on the relative
contribution of these muscle afferents to the circulatory control and the development of central and peripheral
fatigue during exercise. The proposed studies will also examine the impact of HTN on muscle morphometry and
contraction-induced intramuscular (whole muscle and muscle interstitium) metabolic changes, gene expression
and protein levels of metabosensitive receptors on muscle afferents, and the functional impact of these changes
in terms of fatigue. Specifically, we will use lumbar intrathecal fentanyl to block the central projection of group
III/IV muscle afferents during voluntary and passive exercise (no concomitant effect on feedforward drive). This
proven approach will enable us to evaluate and distinguish between the effects of group III and IV muscle
afferents on blood pressure, leg blood flow, and cardiac output during large and small muscle mass exercise
(bicycle and knee-extension), and the development of central and peripheral fatigue (femoral nerve stimulation
techniques). We will also conduct morphometric and metabolite analysis on pre/post-exercise muscle biopsies
and dialysate (resulting from intramuscular microdialysis during exercise) to evaluate alterations in intrinsic
muscle characteristic as a potential factor determining metaboreflex abnormalities in HTN. Furthermore, we will
determine the mRNA and protein levels of ASIC3, P2X, EP4 and TRPV1 receptors in human dorsal root ganglion
neurons of HTN patients and CTRLs. Finally, to determine the specific contribution of these metabosensitive
molecular receptors to the development of central fatigue in HTN and CTRLs, we will perform an intramuscular
infusion of a "metabolite soup" into the unfatigued quadriceps muscle. We have designed the "soup" to
specifically activate ASIC3, P2X, and TRPV1 receptors and have verified it's specificity in published animal and
human studies. Based on recent findings suggesting greater metaboreceptor-mediated reflexes in HTN vs
CTRLs, we expect, following the intramuscular soup infusion, greater central fatigue in HTN vs CTRLs. The
results from this analysis will contribute to a better understanding of the role of metaboreceptors as a potential
mechanism underlying central fatigue and reflex abnormalities characterizing exercising HTN patients.
Combined, this research will provide new insight ...

## Key facts

- **NIH application ID:** 9880308
- **Project number:** 5R01HL116579-08
- **Recipient organization:** UTAH STATE HIGHER EDUCATION SYSTEM--UNIVERSITY OF UTAH
- **Principal Investigator:** MARKUS AMANN
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $381,250
- **Award type:** 5
- **Project period:** 2013-04-01 → 2022-02-28

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9880308

## Citation

> US National Institutes of Health, RePORTER application 9880308, Role of Sensory Neurons in Human Cardiovascular Disease (5R01HL116579-08). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9880308. Licensed CC0.

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