Macquarie University
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Mechanisms underlying the abnormal respiratory-sympathetic phenotype of the Spontaneously Hypertensive Rat

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posted on 2022-12-23, 00:36 authored by Tonique Newbold

There is an established link between sympathetic dysregulation and hypertension, with animal models showing a temporal phase shift in peak sympathetic activity from the postinspiratory (post-I) period to late inspiration. The mechanism driving altered respiratorysympathetic coupling in spontaneously hypertensive rats (SHR) is still unknown. It has been suggested that pathways driving post-I activity are overactive in SHRs, resulting in premature sympathetic activation. Alternatively, it has been suggested that abnormal excitatory connections between inspiratory neurons in PreBötC and the RVLM cause an increase in sympathetic activity during inspiration. This project used electrophysiological nerve recordings to compare vagal and sympathetic nerve activity between SHR and WKY rats. Additionally, larynx muscle movement was recorded using videography to directly measure post-I laryngeal adduction. It was expected that peak vagus activity would also be phase-shifted in SHRs, but results show similar timing of laryngeal adduction and vagal post-I activity in both strains, despite peak sympathetic activity occurring earlier in SHRs. It was also found that WKYs have a temporal phase shift in vagal post-I activity during hypoxemia, while SHRs showed no change. Hypoxemia delays sympathetic activity in SHRs, while the effect in WKYs is variable and shows no consistent pattern. These findings indicate thar sympathetic and vagal post-I activity are separate mechanisms that can be altered independently in response to homeostatic challenge. As vagal post-I activity is not phase shifted in SHRs, this supports the hypothesis that their altered respiratory-sympathetic coupling is due to a mechanism acting on the sympathetic nervous system directly, not one affecting post-I activity in general.


Table of Contents

1. Introduction -- 2. Methods -- 3. Results -- 4. Discussion -- References

Awarding Institution

Macquarie University

Degree Type

Thesis MRes

Department, Centre or School

Macquarie Medical School

Year of Award


Principal Supervisor

Simon McMullan

Additional Supervisor 1

Peter Burke

Additional Supervisor 2

Cara Hildreth


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