Translation of Cardiovascular Control Models: Are ‘resistant hypertension’ patients truly drug resistant and does neuronal dysregulation contribute?

Description

Hypertension is major health problem across the world affecting 30-40% of adults, and its prevalence continues to grow, especially in developing countries. Whilst hypertension is a relative success story of modern pharmacology there are still a number of patients that do not respond well to treatment. The patients are said to have resistant hypertension. The causes of this type of hypertension are unknown, and there are several hypotheses. One possible contributory factor is a dysregulation of neurones controlling the sympathetic system at the paraventricular nucleus of the hypothalamus (PVN). There is a considerable body of knowledge of the control mechanisms of PVN cardiovascular control neurones in animal models of cardiovascular control and in this project the student will use this knowledge to make predictions about cardiovascular responses that would be expected if resistant hypertensives do indeed have dysregulated sympathetic control circuitry. These predictions will then be tested with patients and controls.

The work will include such measurements as blood pressure, respiration, heart rate and its variability (“HRV”), spontaneous baroreceptor reflexes and forelimb blood flow and their responses to day night cycle, water ingestion, routine medications and postural change in patients and controls. The work will have a strong component of mathematical analysis, including cutting edge mathematical modelling and computer simulations.

The successful applicant will be a science, veterinary or medical graduate with some knowledge of cardiovascular biology. They will be have a fascination with physiological mechanisms and enthusiasm for public engagement.

Training will be given in systemic investigation of human cardiovascular assessment, as well as cutting edge mathematical modelling and computer simulations. This will complement the experience in cardiovascular biology the candidate would, preferably, already have. Formal training on biostatistics will be undertaken at University of Liverpool and further support will be provided in the department.

The Institute of Ageing and Chronic Disease is fully committed to promoting gender equality in all activities. In recruitment we emphasize the supportive nature of the working environment and the flexible family support that the University provides. The Institute holds a silver Athena SWAN award in recognition of on-going commitment to ensuring that the Athena SWAN principles are embedded in its activities and strategic initiatives.

Please note this application will close once a suitable candidate is found. Early applications are encouraged. 

To apply: please send your CV and a covering letter to with a copy to

Availability

Open to students worldwide

Funding information

Self-funded project

Please note there is NO FUNDING attached to this project. In addition to full funding of fees and stipend, we would require approximately £10,000 per year for running costs.

Supervisors

References

Shantsila, A., McIntyre, D. B., Lip, G. Y. H., Fadel, P. J., Paton, J. F. R., Pickering, A. E., & Fisher, J. P. (2015). Influence of age on respiratory modulation of muscle sympathetic nerve activity, blood pressure and baroreflex function in humans. Experimental Physiology, 100(9), 1039–51. http://doi.org/10.1113/EP085071


PM Kearney, M Whelton, K Reynolds, P Muntner, PK Whelton, J He, Global burden of hypertension: analysis of worldwide data. Lancet, 365 (2005), pp. 217-223.


N Nunn, M Womack, C Dart, and R Barrett-Jolley, Function and Pharmacology of Spinally-Projecting Sympathetic Pre-Autonomic Neurones in the Paraventricular Nucleus of the Hypothalamus 

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