Professor Sergey Kasparov

Summary

We work closely with Professor Julian Paton to investigate the roles of angiotensin II, nitric oxide and the neurotransmitter GABA, in the central control mechanisms responsible for maintaining blood pressure at normal levels.

It is vital that blood pressure is tightly regulated in order to supply all major organs with blood. `Essential hypertension' describes the condition where blood pressure is higher than normal over a prolonged period of time. This can lead to atherosclerosis, retinopathy, kidney disease, myocardial infarction and stroke.

Angiotensin II is a peptide that acts on blood vessel walls to modify arterial pressure. Blocking its action brings about a reduction in blood pressure; angiotensin II antagonists are standard drugs in the treatment of hypertension.

We have found that angiotensin II not only affects vessel walls, but also plays an important role in the brainstem. One part of the brainstem, the Nucleus of the Solitary Tract (NTS), exerts control over blood pressure via the `arterial baroreceptor reflex', a feedback loop that returns levels to normal if arterial pressure increases. Angiotensin II leads to inhibition of this reflex. It stimulates the release of nitric oxide, which in turn increases release of inhibitory transmitter GABA, GABA then inhibits the reflex and prevents lowering of blood pressure.

We use a variety of techniques, including viral gene transfer, high-resolution confocal imaging and electrophysiology. By using an experimental design that combines molecular, cellular, imaging, whole system and electrophysiological methods, we are able to draw reliable conclusions about the physiology of blood pressure regulation. This is only possible by applying an integrative and interdisciplinary approach.

Through understanding the details of these mechanisms and how they may be reversed, possibilities will be opened for developing more effective treatment of essential hypertension.

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Activities / Findings

• Central effects of angiotensin II
• Central Angiotensin II & Arterial Pressure Control
• Targeting of specific physiological phenotypes of NTS neurones
• GABAergic transmission in NTS.

Teaching

Medicine year 1:

• Cell and its organelles
• Cell division and cells as components of tissue
• Intercellular communication
• Autonomic nervous system
• Endocrine system
• Homeostasis 

Medicine year 2 tutorials:

• Respiration
• Renal
• GI tract
• Neurophysiology

Science year 2:

• Introduction to DNA 

Keywords

• blood pressure
• brainstem
• angiotensin II
• nitric oxide
• viral transfection
• imaging
• GFP
• baroreceptor
• neurogenic
• electrophysiology

Skills

• Stroke
• retinopathy
• hypertension
• kidney disease
• mycardial infarction
• atherosclerosis

Processes and functions

• Blood pressure regulation
• homeostasis
• processing information in the brainstem
• brainstem control mechanisms

Methodologies

• Confocal microscopy
• viral transvection
• adenoviral
• lentiviral
• in vitro slices
• imaging
• fluorescence microscopy
• electrophysiology

Memberships

Organisations

School of Physiology and Pharmacology

Other sites

• Bhi
• Medical-school
• Neuroscience

Research Areas

• Molecular Neuroscience
• 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
• Kasimov, V, Larina, O, Castaldo, C, Marina, N, Patrushev, M, Kasparov, S & Gourine, A 2013, ‘Differential sensitivity of brainstem vs cortical astrocytes to changes in pH reveals functional regional specialization of astroglia’. J. Neurosci, vol 33., pp. 435-441
• Marina, N, Tang, F, Figueiredo, M, Mastitskaya, S, Kasimov, V, Mohamed-Ali, V, Roloff, E, Teschemacher, AG, Gourine, AV & Kasparov, S 2013, ‘Purinergic signalling in the rostral ventro-lateral medulla controls sympathetic drive and contributes to the progression of heart failure following myocardial infarction in rats’. Basic Research in Cardiology, vol 108., pp. 317
• Mastitskaya, S, Marina, N, Gourine, A, Gilbey, MP, Spyer, KM, Teschemacher, AG, Kasparov, S, Trapp, S, Ackland, GL & Gourine, AV 2012, ‘Cardioprotection evoked by remote ischaemic preconditioning is critically dependent on the activity of vagal pre-ganglionic neurones’. Cardiovascular research, vol 95., pp. 487-494
• Figueiredo, M, Lane, S, Tang, F, Liu, B, Hewinson, J, Marina, N, Kasymov, V, Souslova, E, Chudakov, D, Gourine, A, Teschemacher, A & Kasparov, S 2011, ‘Optogenetic experimentation on astrocytes’. Experimental Physiology, vol 96(1)., pp. 40 - 50
• Yao, S, Antunes, VR, Bradley, P, Kasparov, S, Ueta, Y, Paton, J & Murphy, D 2011, ‘Temporal profile of arginine vasopressin release from the neurohypophysis in response to hypertonic saline and hypotension measured using a fluorescent fusion protein’. Journal of Neuroscience Methods, vol 201., pp. 191 - 195
• Kasparov, S 2011, ‘Glial-neuronal interactions in the central nervous cardiovascular and respiratory control’. Exp Physiol, vol 96., pp. 391 - 392
• Liu, B, Hewinson, J, Montero, F, Sunico, CR, Portillo, F, Paton, J, Moreno-Lopez, B & Kasparov, S 2011, ‘NOS antagonism using viral vectors as an experimental strategy: implications for in vivo studies of cardiovascular control and peripheral neuropathies’. Methods Mol Biol, vol 704., pp. 197 - 223
• Kasparov, S 2011, ‘The many facets of optogenetics. Introduction’. Exp Physiol, vol 96., pp. 1 - 3
• Gourine, AV & Kasparov, S 2011, ‘Astrocytes as brain interoceptors’. Exp Physiol, vol 96., pp. 411 - 416

View complete publications list in the University of Bristol publications system

Networks & contacts

• Professor Julian Paton - University of Bristol