# Role of presympathetic neurons of the hindbrain in cardiovascular control

> **NIH NIH R01** · UNIVERSITY OF VIRGINIA · 2021 · $542,756

## Abstract

Contact PD/PI: Abbott, Stephen
Project summary
Hypertension is an important risk factor for the development of cardiovascular disease. Despite major
therapeutic advances, hypertension is often treatment resistant and still causes countless deaths from stroke
and heart disease. Hypertension may be neurogenic i.e. it is associated with and probably caused by a chronic
elevation of sympathetic nerve activity (SNA). This SNA elevation has many suspected causes such as an
increase in carotid body activity, brainstem hypoxemia and CNS oxidative stress but the CNS network that
ultimately mediates the SNA elevation is not well understood. One reason is our limited understanding of the
connections and function of most brainstem pathways implicated in the generation of SNA.
This proposal focuses on the contribution of the A5 group of hindbrain noradrenergic neurons to the
regulation of SNA and
blood pressure (BP). This choice is motivated by four considerations. First, A5 neurons
are the main source of noradrenergic input to sympathetic preganglionic neurons. Second, noradrenaline
exerts powerful excitatory effects on sympathetic preganglionic neurons. Third, A5 neurons are strongly
activated by hypoxia and therefore could mediate some of the effects of hypoxia on SNA and contribute to the
adaptive changes elicited by hypoxia. Lastly, the efflux of noradrenaline metabolites from the brain of
hypertensive humans (MHPG) is elevated, which suggests that CNS NA-release may be abnormally high.
These four considerations suggest that A5 neurons hyperactivity could contribute to neurogenic hypertension.
I will test the hypothesis that A5 noradrenergic cells activate the sympathetic nervous system by exciting
sympathetic preganglionic neurons via NA-release. Second, I propose to determine the transcriptome and
connectome of A5 neurons, and compare them with that of neighboring neurons that control BP in the rostral
ventrolateral medulla. And finally, I will test whether
A5-dependent NA-release
causes
sympathetic
hyperactivity in
a model of sleep apnea (acute intermittent hypoxia). Understanding the hindbrain networks
controlling the sympathetic system may benefit the treatment of any condition associated with sympathetic
dysfunction, like neurogenic hypertension, heart failure and multiple systems atrophy.
Page 6
Project Summary/Abstract

## Key facts

- **NIH application ID:** 10116460
- **Project number:** 5R01HL148004-03
- **Recipient organization:** UNIVERSITY OF VIRGINIA
- **Principal Investigator:** Stephen Abbott
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $542,756
- **Award type:** 5
- **Project period:** 2019-06-10 → 2024-02-28

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10116460

## Citation

> US National Institutes of Health, RePORTER application 10116460, Role of presympathetic neurons of the hindbrain in cardiovascular control (5R01HL148004-03). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10116460. Licensed CC0.

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