Professor Julian Paton

Summary

Paton’s group seeks to understand what changes within the central nervous system during the aetiology of neurogenic hypertension. Sympathetic nerve activity destined for the heart and arterioles is elevated prior to the onset of hypertension, which is suggestive of a causative role. In hypertension, cerebral vascular resistance is elevated causing brain hypoperfusion – a well known stimulant of sympathetic activity and hypertension. The microvasculature of the brainstem is also inflamed.

The hypothesis of elevated brainstem vascular resistance and inflammation as causative to hypertension is being explored in animal models and human patients. Transcriptomic analysis of brainstem genes altered in hypertension has led to exciting novel targets that are being validated with virally mediated transgenesis, stem cell transplantation, optogenetics and radio-telemetry in vivo.

The group’s interest in mechanisms of central respiratory pattern generation has led to the observation that its modulation of sympathetic outflow is enhanced in hypertension. Additionally, data has shed light on plausible reasons for respiratory arrhythmias such as: sudden infant death and Rett syndromes. Data are being used to make mathematical models to assist in the further understanding of brainstem function as well as contributing to the Human Physiome project. A number of clinical translational studies driven by hypotheses gleaned from basic animal research are now underway in hypertensive patients.

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Activities / Findings

• 1995-1996: Invention of a “tour de force” integrative physiological in situ working heart- brainstem preparation. This allowed studies we could not have done previously.
• 1998-2002: In collaboration with Professor Sergey Kasparov, we revealed that brainstem actions of angiotensin II, a peptide associated with hypertension, were mediated by liberation of nitric oxide from the endothelium leading to a novel form of brain signalling: vascular-neuronal signalling.
• 2003: We provided unequivocal evidence that vascular-neuronal signalling in the brainstem contributed to high blood pressure levels in an animal model of hypertension.
• 2006-present: Discovery that brainstem pacemaker activity was essential for gasping. This and other work dives our mathematical modelling which contributes to the Human Physiome Project.
• 2007- present: In collaboration with Professor David Murphy, we identified unique genes within brain regions regulating arterial pressure thereby providing unique clues as to those that may generate neurogenic hypertension.
• 2007: We discovered that the brainstem vasculature was inflamed in the hypertensive brain.
• 2007: In collaboration with Professors Jeff Smith (NINDS, NIH) and Ilya Rybak (Drexel University), we revealed the precise compartments of the brainstem for generation of distinct respiratory patterns and the conditions and mechanisms for expression of these different rhythms.

2009: In collaboration with Dr Andrew Allen (Melbourne University) and Dr Anthony Pickering, we discovered that enhanced sympathetic activity precedes the onset of hypertension and is dependent on exacerbated modulation by the brainstem respiratory pattern generator.

Teaching

• Respiratory physiology to Veterinary, Medical and Science students.
• Respiratory practical classes. 
• Third year honours element organiser on the Cardiovascular System in Health and Disease.
• Cardiovascular physiology to stage III honours physiology students
• Molecular Neuroscience course
• Lectures on cardiovascular physiology to students at the University of Oxford.

Keywords

• Brainstem
• autonomic nervous system
• sympathetic activity
• blood pressure
• breathing
• baroreceptor
• chemoreceptor
• reflexes
• bladder

Skills

• Hypertension
• neurovascular disease
• cerebral artery stenosis
• SIDS
• Rett syndrome
• heart failure

Processes and functions

• Autonomic nervous system function
• homeostatic reflexes

Methodologies

• Neurophysiology
• patch clamp
• imaging
• fMRI
• microneurography
• in vivo gene transfer
• lentivirus
• adenovirus
• stem cell

Memberships

Organisations

School of Physiology and Pharmacology

Other sites

• Bhi
• Neuroscience

Research Areas

• CNS and hypertension

Research Themes

• Cardiovascular Research

Links

•   home page

Recent publications

• Waki, H, Hendy, EB, Hindmarch, CCT, Gouraud, S, Toward, M, Kasparov, S, Murphy, D & Paton, JFR 2013, ‘Excessive leukotriene B4 in nucleus tractus solitarii is prohypertensive in spontaneously hypertensive rats’. Hypertension, vol 61., pp. 194-201
• Paton, JFR, Sobotka, PA, Fudim, M, Engleman, ZJ, Hart, ECJ, McBryde, FD, Abdala, AP, Marina, N, Gourine, AV, Lobo, M, Patel, N, Burchell, A, Ratcliffe, LEK & Nightingale, A 2013, ‘The carotid body as a therapeutic target for the treatment of sympathetically mediated diseases’. Hypertension, vol 61., pp. 5-13
• Ruchaya, PJ, Paton, JFR, Murphy, D & Yao, ST 2012, ‘A cardiovascular role for fractalkine and its cognate receptor, CX3CR1, in the rat nucleus of the solitary tract’. Neuroscience, vol 209., pp. 119-27
• Yao, S, Gouraud, SSS, Qiu, J, Paton, JFR & Murphy, D 2012, ‘Selective up-regulation of JunD transcript and protein expression in vasopressinergic supraoptic nucleus (SON) neurones in water deprived rats.’. J Neuroendocrinol.
• Murphy, D, Konopacka, A, Hindmarch, C, Paton, JFR, Sweedler, JV, Gillette, MU, Ueta, Y, Grinevich, V, Lozic, M & Japundzic-Zigon, N 2012, ‘The hypothalamic-neurohypophyseal system: from genome to physiology’. Journal of neuroendocrinology, vol 24., pp. 539-53
• Toward, MA, Abdala, AP, Knopp, SJ, Paton, JFR & Bissonnette, JM 2012, ‘Increasing brain serotonin corrects CO2 chemosensitivity in methyl-CpG-binding protein 2 (Mecp2) deficient mice’. Experimental Physiology.
• Abdala, AP, McBryde, FD, Marina, N, Hendy, EB, Engelman, ZJ, Fudim, M, Sobotka, PA, Gourine, AV & Paton, JFR 2012, ‘Hypertension is critically dependent on the carotid body input in the spontaneously hypertensive rat’. The Journal of Physiology, vol 590., pp. 4269-77
• Rybak, IA, Molkov, YI, Paton, JF, Abdala, AP & Zoccal, DB 2012, ‘Chapter 143 - Modeling the Autonomic Nervous System’. in: David Robertson, Italo Biaggioni, Geoffrey Burnstock, Phillip A Low, Julian FR Paton (eds) Primer on the Autonomic Nervous System (Third Edition). Academic Press, Loss Angeles, pp. 681 - 687
• McAllen, RM, Salo, LM, Paton, J & Pickering, A 2011, ‘Processing of central and reflex vagal drives by rat cardiac ganglion neurones: an intracellular analysis’. Journal of Physiology, vol 589., pp. 5801 - 5818
• Kenny, D, Polson, J, Martin, R, Caputo, M, Wilson, D, Cockroft, J, Paton, J & Wolf, A 2011, ‘Relationship of aortic pulse wave velocity and baroreceptor reflex sensitivity to blood pressure control in patients with repaired coarctation of the aorta’. Am Heart J, vol 162(2)., pp. 398 - 404

View complete publications list in the University of Bristol publications system

Networks & contacts

• Bristol:
  Prof Raimondo Ascione (Bristol Heart Institute)
  Dr Andreas Baumbach (Bristol Heart Institute)
  Prof Alan Champneys (Mathematical Engineering)
  Dr Kimberly Connor (Physiology & Pharmacology)
  Dr David Cussans (Physics)
  Prof S Kasparov (Physiology & Pharmacology)
  Dr Patrick Kehoe (Frenchay - Bristol)
  Dr Philip Langton (Physiology & Pharmacology)
  Professor Seth Love (frenchay Hospital - Bristol)
  Dr Angus Nightingale (Bristol Heart Institute)
  Prof. D. Murphy (LINE - Bristol)
  Prof David Newbold (Physics - Bristol)
  Mr N Patel (Frenchay Hospital - Bristol - UK)
  National
  Dr G S Bewick - Department of Physiology - University of Aberdeen
  Dr Mark Dewhurst - Pfizer UK - Kent
  Dr M Dutschmann - Physiology - University of Leeds
  International:
  Dr A Allen - Department of Phjysiology - University of Melbourne - Melbourne
• Australia
  Prof John Bissonnette (Physiology - University of Oregon - USA)
  Dr Derek Leishman - Lilly - USA
  Prof B Machado - Univ Sao-Paulo - Riberao Preto - Brazil
  Prof R McAllen - Howard Florey Institute - Melbourne - Australia
  Dr D Mayorov