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Respiratory sympathetic coupling in chronic kidney disease

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posted on 28.03.2022, 16:50 authored by Manash Saha
Chronic kidney disease (CKD) is a major public health problem, resulting in significant morbidity and mortality. Among the different causes and comorbidities of CKD, hypertension draws special attention as it is often difficult to treat and increases cardiovascular risk in these patients. It has been established that sympathetic nerve activity (SNA) is increased in hypertension and CKD. Recent works suggest that respiratory modulation of SNA [respiratory sympathetic coupling (respSNA); the coordination between breathing and SNA] is a driving factor behind increased SNA in a number of diseased states including hypertension; however, the pattern of respSNA with its role in underlying mechanism in CKD is not yet known. Accordingly, the aims of the thesis were to (i) determine if respSNA is altered in a classical rat model of CKD, the Lewis Polycystic Kidney (LPK) rat and determine if this is associated with hypersensitivity of peripheral chemoreceptors; (ii) identify if the pattern of respSNA along with its association with peripheral chemoreceptors is different between male and female animals with CKD; (iii) examine if respSNA contributes to baroreflex dysfunction in CKD and (iv) to investigate if bilateral carotid sinus (CSN) transection, a method by which to prevent peripheral chemoreceptors input, results in reduction of respSNA and blood pressure in the LPK rat. The main finding was that the male LPK rats had amplified respSNA compared to Lewis control rats since very early age (5 weeks). Notably, peripheral chemoreceptor stimulation revealed more enhanced respSNA in both juvenile and adult LPK rats. The female LPK rats also exhibited amplified respSNA compared to female Lewis rats. Another significant finding was that inhibition of altered respSNA selectively improved the baroreflex response of SNA in LPK rats. Furthermore, transection of CSN decreased blood pressure in the LPK model of CKD, although respSNA was elevated in LPK rats that had undergone CSN transection compared to controls. The results help us to understand the basic linking between SNA and respiration, with the goal of targeting peripheral chemoreceptors and respSNA for novel therapies for hypertension associated with CKD.

History

Table of Contents

1. Literature review -- 2. Respiratory sympathetic modulation is augmented in chronic kidney disease -- 3. Sex does not affect augmented respiratory sympathetic modulation in a rodent model of chronic kidney disease -- 4. Reducing respiratory sympathetic coupling selectively improves baroreflex function in a rodent model of chronic kidney disease -- 5. Attenuation of high blood pressure in an animal model of chronic kidney disease after bilateral carotid sinus nerve transection -- 6. Final discussion -- 7. References -- 8. Appendix.

Notes

Bibliography: 155-209 Empirical thesis.

Awarding Institution

Macquarie University

Degree Type

Thesis PhD

Degree

PhD, Macquarie University, Faculty of Medicine and Health Sciences, Department of Biomedical Sciences

Department, Centre or School

Department of Biomedical Sciences

Year of Award

2019

Principal Supervisor

Jacqueline Phillips

Additional Supervisor 1

Cara Margaret Hildreth

Additional Supervisor 2

Qi-Jian Sun

Rights

Copyright Manash Saha 2019. Copyright disclaimer: http://mq.edu.au/library/copyright

Language

English

Extent

1 online resource (xviii, 209, ix pages) graphs, tables

Former Identifiers

mq:72091 http://hdl.handle.net/1959.14/1281292