01whole.pdf (2.08 MB)
Download file

Hypertension in an animal model of polycystic kidney disease is not dependent on the short-term actions of endogenous tumour necrosis factor-α in the subfornical organ

Download (2.08 MB)
thesis
posted on 28.03.2022, 17:39 by Monique Van Acquoy
The development of hypertension in an animal model of polycystic kidney disease, the Lewis polycystic kidney (LPK) rat, is caused, in part, by the overactivation of the subfornical organ (SFO). Circulating proinflammatory cytokines, namely tumour necrosis factor-α (TNFα), are suggested to act in the central nervous system to produce an increase in neuronal excitability. Therefore, we hypothesised that TNFα acts on the SFO to increase neuronal activity, therefore contributing to the development of hypertension. Urethane-anaesthetised Lewis control (n=20 total) and LPK (n=19 total) animals underwent microinjections of TNFα or tumour necrosis factor receptor 1 antibody (TNFRI Ab) or minocycline, an inhibitor of microglial activation, followed by a GABAa agonist into the SFO. Microglial activation in the SFO was assessed by staining with an anti-Iba1 antibody (n=2 Lewis and n=3 LPK). Microinjection of TNFα into the SFO led to a dose-dependent increase in mean arterial pressure (MAP) in Lewis animals (P0.05). Minocycline microinjection did not reduce MAP in Lewis or LPK animals (-1 ± 1 mmHg vs -1 ± 1 mmHg, Lewis vs LPK, P>0.05). Microinjection of minocycline in LPK animals significantly increased the tonic activation of the SFO, indicated by the increased depressor response to GABAa agonist microinjection (-12 ± 2 mmHg vs -23 ± 4 mmHg, no inhibitor vs prior minocycline microinjection, P=0.04). Preliminary observation suggests that LPK animals have considerably more activated microglia than Lewis animals. Overall, these findings demonstrate that proinflammatory cytokines in the SFO do not contribute to the short-term control of BP in normotensive conditions and do not contribute to the overactivation and therefore the development of hypertension in LPK animals -- abstract.

History

Table of Contents

1. Introduction -- 2. Methods -- 3. Results -- 4. Discussion -- 5. Conclusion -- References -- Appendix.

Notes

Theoretical thesis. Bibliography: pages 61-72

Awarding Institution

Macquarie University

Degree Type

Thesis MRes

Degree

MRes, 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

Cara M. Hildreth

Additional Supervisor 1

Jacqueline K. Phillips

Rights

Copyright Monique Van Acquoy 2019. Copyright disclaimer: http://mq.edu.au/library/copyright

Language

English

Extent

1 online resource (x, 73 pages) diagrams, graphs, tables

Former Identifiers

mq:71864 http://hdl.handle.net/1959.14/1278885