# Peripheral Sympathetic Dysfunction in Cardiac Disease

> **NIH NIH R01** · OREGON HEALTH & SCIENCE UNIVERSITY · 2024 · $700,140

## Abstract

Hypertension and heart failure increase risk for ventricular arrhythmias and sudden cardiac death. Autonomic
dysregulation and sympathetic hyperactivity accompany these diseases and trigger lethal arrhythmias.
Interventions that target the central nervous system to inhibit sympathetic outflow have not been effective in
prolonging life in patients, whereas interventions that target the periphery (beta blockers, ganglionectomy)
decrease arrhythmias and prolong life. We hypothesize that central nervous system activity is amplified by post-
ganglionic neurons in cardiovascular disease to enhance cardiac sympathetic transmission which contributes to
pathology. During the previous period of support, we showed that noradrenergic sympathetic neurons have
excitatory cholinergic collateral projections. Preliminary data indicate that hypertension causes a significant
increase in cardiac sympathetic neuron activity. Additional data indicate that cholinergic collateral transmission
is required for the development of hyperactivity in cardiac sympathetic neurons, and that increased collateral
transmission is involved. In Aim 1 we will determine if hypertension increases sympathetic neuron activity
generally, or if the increased activity is limited to cardiac neurons, and if collateral signaling is required. In Aim 2
we will investigate the mechanisms by which cholinergic collateral transmission is elevated in hypertension. New
data from multiple labs implicate satellite glial cells as important regulators of sympathetic neuronal activity. In
Aim 3 we will determine if activation of satellite glial cells in sympathetic ganglia plays a role in sympathetic
hyperactivity in disease. We have assembled a team of accomplished experts, key animal models, and powerful
genetic tools to accomplish these studies. We expect that novel insights and targets for therapeutic intervention
will come from the studies described here, and that this work with have implications for treatment of the many
diseases characterized by high sympathetic activation.

## Key facts

- **NIH application ID:** 10980210
- **Project number:** 2R01HL146833-05
- **Recipient organization:** OREGON HEALTH & SCIENCE UNIVERSITY
- **Principal Investigator:** BETH A HABECKER
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $700,140
- **Award type:** 2
- **Project period:** 2020-04-01 → 2028-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10980210

## Citation

> US National Institutes of Health, RePORTER application 10980210, Peripheral Sympathetic Dysfunction in Cardiac Disease (2R01HL146833-05). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10980210. Licensed CC0.

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