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Professor Julian Paton Brainstem control mechanisms in blood pressure regulation Full contact details |
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Projects - Diseases - Processes - Techniques - Equipment - Funding - Collaborations - Group members - Publications & further information
Research
Our interests lie in brainstem control of blood pressure.
Chronically elevated blood pressure - hypertension- is asymptomatic, and contributes to atherosclerosis, kidney disease, retinopathy and stroke. An important aspect of the condition is the role played by the brainstem - `neurogenic hypertension'.
One way that the brainstem acts is through the baroreceptor reflex. This feedback loop performs short-term, minute-by-minute control of blood pressure.
We have found evidence that the brainstem is also involved in changes over longer timescales. Such changes appear to be mediated by angiotensin II & nitric oxide. In peripheral blood vessels these are vasoconstrictive and vasodilatory respectively, acting antagonistically to vary vasomotor tone and hence maintain blood pressure at stable levels.
Recently, it has been found that angiotensin II is also produced in the brain. High levels lead to a rise in blood pressure. At present, it is unclear how it affects brainstem neuronal circuitry regulating arterial pressure & the baroreceptor reflex. We have found that angiotensin II can trigger release of nitric oxide from blood vessels localised to a region of the brainstem controlling blood pressure.
We are investigating this mechanism using viral transfection methods. We can study effects of chronically altering the production of nitric oxide at cellular, whole system & behavioural levels. We believe this multidisciplinary approach is the only way to properly evaluate the physiological control of blood pressure.
By applying this experimental approach in a hypertensive model, we have found that manipulating the actions of angiotensin II & nitric oxide in a highly restricted part of the brainstem can return blood pressure to a normal level.
These findings indicate that the conventional wisdom, that brainstem circuitry is only involved in minute-to-minute control of blood presssure, may have to be reconsidered.
- Sources of nitric oxide in the Nucleus of the Solitary Tract (NTS) and mechanisms of its generation
- Mechanisms of angiotensin II on cardiorespiratory function using gene transfer.
- Identification of specific promoters for expression in endothelial cells.
- Dominant negative inhibition of endotheleial nitric oxide synthase using lentiviral transfection methods.
Stroke, retinopathy, hypertension, kidney disease, mycardial infarction, atherosclerosis
Confocal imaging, GFP and fluorescence microscopy, viral gene transfer, adenoviral transfection, in vitro slice methods, molecular biological methods, electrophysiology.
Confocal microscope, electrophysiological recording apparatus
Projects - Diseases - Processes - Techniques - Equipment - Funding - Collaborations - Group members - Publications & further information
Grants and funding
- 2001 - BBSRC-JREI
- 2001 - Nuffield Project grant
- 2001 - MRC Priority Area PhD Studentship
- 2001 - American Physiological Society Collaborative Travel Fund
- 2001 - Merck Sharp & Dohme;
- 2000 - Wellcome Trust - Joint Infrastructure Fund
- 2000 -Wellcome Trust Project grant
Collaborations
- Dr J. Deuchars, University of Leeds
- Professor M Raizada, University of Florida, USA
- Professor K.M. Spyer, Royal Free Hospital, London
- Professor P.M. Headley, University of Bristol
- Dr S. Kasparov, University of Bristol
- Professor D. Murphy, University of Bristol
- Professor A. Wolf, Department of Anaesthesiology, Bristol
Publications, recommended reading and further information
Selected recent publications:
Hidefumi Waki, Beihui Liu, Masao Miyake, Kiyoaki Katahira, David Murphy, Sergey Kasparov, and Julian F.R. Paton. (2007)
Functional Adhesion Molecule-1 Is Upregulated in Spontaneously Hypertensive Rats. Evidence for a Prohypertensive Role Within the Brain Stem
Published online in Hypertension, doi:10.1161/HYPERTENSIONAHA.106.085589
Wang, S., Paton J.F.R. & Kasparov, S. (2007).
Differential sensitivity of excitatory and inhibitory synaptic transmission to modulaton by nitric oxide in the nucleus tractus solitarii.
Experimental Physiology, [Epub ahead of print]
Simms, A., Paton, J.F.R & Pickering, A.E.S. (2007).
Hierarchical recruitment of the sympathetic and parasympathetic limbs of the baroreflex in normotensive and spontaneously hypertensive rats.
Journal of Physiology, 579.2, 473-486
Paton, J.F.R., Abdala, A.P.L., Koizumi, H. & Smith, J.C. & St.-John W.M. (2006)
Respiratory rhythm generation during gasping depends on persistent sodium current.
Nature Neuroscience, 9 , 311-313.
Potts, J.T., Rybak, I.A. & Paton, J.F.R. (2005).
Role of the dorso-lateral pons in mediating phrenic nerve entrainment following contraction of skeletal muscle.
Journal of Neuroscience 25 , 1965-1978 .
Further background reading:
Paton JF, Boscan P, Murphy D, Kasparov S, 2001
Acta Physiol Scand. 173(1) 127-37
Unravelling mechanisms of action of angiotensin II on cardiorespiratory
function using gene transfer.
Kasparov S, Paton JF. 2000
Exp Physiol. 85(6 747-55.
Somatic gene transfer: implications for cardiovascular control.
Webpage on Physiology and Pharmacology Department website
Projects - Diseases - Processes - Techniques - Equipment - Funding - Collaborations - Group members - Publications & further information