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Professor Julian Paton
Professor Julian Paton
Professorial Research Fellow in Physiology
Area of research
Mechanisms of neurogenic hypertension
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.
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.
- 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.
- autonomic nervous system
- sympathetic activity
- blood pressure
- neurovascular disease
- cerebral artery stenosis
- Rett syndrome
- heart failure
Processes and functions
- Autonomic nervous system function
- homeostatic reflexes
- patch clamp
- in vivo gene transfer
- stem cell
- Narkiewicz, K, Ratcliffe, L, Hart, E, Briant, L, Chrostowska, M, Wolf, J, Szyndler, A, Hering, D, Sheikh, AAA, Manghat, NE, Burchell, A, Durant, C, Lobos, MD, Sobotka, PA, Patel, N, Leiter, JC, Engelman, ZJ, Nightingale, A & Paton, J, 2016, Unilateral carotid body resection in resistant hypertension: A safety and feasibility trial. Journal of the American College of Cardiology, vol 1., pp. 313-324
- Barnett, WH, Abdala, AP, Paton, JF, Rybak, IA, Zoccal, DB & Molkov, YI, 2016, Chemoreception and neuroplasticity in respiratory circuits. Experimental Neurology.
- Paton, J, Rodrigues, J, Hart, E & Bucciarelli-Ducci, C, 2016, Comprehensive characterisation of hypertensive heart disease left ventricular phenotypes. Heart.
- McBryde, FD, Malpas, SC & Paton, J, 2016, Intracranial mechanisms for preserving brain blood flow in health and disease. Acta Psychologica.
- Pijacka, W, Moraes, DJDA, Ratcliffe, LEK, Nightingale, AK, Hart, ECJ, Silva, Md, Machado, B, McBryde, FD, Sheikh, APA, Ford, A & Paton, JFR, 2016, Purinergic receptors in the carotid body as a new drug target for controlling hypertension. Nature Medicine.
- Rodrigues, JCL, Rohan, S, Dastidar, AG, Trickey, A, Szantho, G, Ratcliffe, LEK, Burchell, AE, Hart, EC, Bucciarelli-Ducci, C, Hamilton, MCK, Nightingale, AK, Paton, JFR, Manghat, NE & MacIver, DH, 2016, The relationship between left ventricular wall thickness, myocardial shortening and ejection fraction in hypertensive heart disease: insights from cardiac magnetic resonance: LVH independently augments EF in hypertension. Journal of Clinical Hypertension.
- Rodrigues, JCL, Rohan, S, Dastidar, AG, Harries, I, Lawton, CB, Ratcliffe, LE, Burchell, AE, Hart, EC, Hamilton, MCK, Paton, JFR, Nightingale, AK & Manghat, NE, 2016, Hypertensive heart disease versus hypertrophic cardiomyopathy: multi-parametric cardiovascular magnetic resonance discriminators when end-diastolic wall thickness ≥ 15 mm. European Radiology.
- Briant, LJB, Burchell, AE, Ratcliffe, LEK, Charkoudian, N, Nightingale, AK, Paton, JFR, Joyner, MJ & Hart, EC, 2016, Quantifying sympathetic neuro-haemodynamic transduction at rest in humans: Insights into sex, ageing and blood pressure control. Journal of Physiology, vol 594., pp. 4753-4768
- Burchell, AE, Rodrigues, JCL, Charalambos, M, Ratcliffe, L, Hart, E, Paton, J, Baumbach, A, Manghat, NE & Nightingale, A, 2016, Comprehensive first-line magnetic resonance imaging in hypertension: Experience from a single centre tertiary referral clinic. Journal of Clinical Hypertension.
- Hendy, E, Marvar, P, Cruise, T, Walas, D, DeCicco, D, Vadigepalli, R, Schwaber, J, Waki, H, Murphy, D & Paton, JFR, 2016, Systemic leukotriene b4 receptor antagonism lowers arterial blood pressure and improves autonomic function in the spontaneously hypertensive rat. Journal of Physiology.
Networks & contacts
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)
Dr G S Bewick - Department of Physiology - University of Aberdeen
Dr Mark Dewhurst - Pfizer UK - Kent
Dr M Dutschmann - Physiology - University of Leeds
Dr A Allen - Department of Phjysiology - University of Melbourne - Melbourne
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
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