Sympathetic Nervous System Activation In Renal Failure. Its Contribution To Pathogenesis And Progression.
Funder
National Health and Medical Research Council
Funding Amount
$490,796.00
Summary
Cardiovascular morbidity and mortality is exceedingly high in patients with chronic renal failure and particularly end stage renal disease. Recent studies suggest that sympathetic activation contributes substantially to the development of hypertension, progression of renal disease and cardiovascular prognosis in these patients. Increased sympathetic nerve firing has been demonstrated in end stage renal disease by the use of clinical microneurography, which has been attributed to uremia-related t ....Cardiovascular morbidity and mortality is exceedingly high in patients with chronic renal failure and particularly end stage renal disease. Recent studies suggest that sympathetic activation contributes substantially to the development of hypertension, progression of renal disease and cardiovascular prognosis in these patients. Increased sympathetic nerve firing has been demonstrated in end stage renal disease by the use of clinical microneurography, which has been attributed to uremia-related toxins. However, renal transplant recipients with excellent graft function and no signs of uremia still exhibit increased sympathetic nerve firing. Most interestingly, bilateral nephrectomized patients have nerve firing rates comparable to that of normal control subjects without renal disease. These data suggest that the diseased kidneys exert excitatory effects on the sympathetic nervous system independent of correction of uremia. The proposed study aims to comprehensively investigate the pattern of sympathetic activation both centrally (microneurography) and regionally (radiotracer dilution methodology) in patients with chronic renal failure and end stage renal disease . The effect of the centrally acting sympatholytic drug rilmenidine on sympathetic activity in the setting of renal disease will be assessed. Patients with ESRD waitlisted for kidney transplantation will be studied before and after transplantation. Some of the transplant recipients will also have undergone uni- or bilateral nephrectomy before transplantation which will enable us to further explore the role of the diseased kidneys in sympathetic activation. The results of this study may prove to have significant implications for treatment and prevention of cardiovascular morbid events frequently associated with renal disease.Read moreRead less
Light, Sound And Touch Influence The Autonomic Nervous System Via A Non-canonical Pathway
Funder
National Health and Medical Research Council
Funding Amount
$329,666.00
Summary
We examine a recently discovered brain circuit through which visual and acoustic stimuli can interact with the neural systems that control breathing, blood pressure and heart rate. The outcomes of this project will characterise a pathway by which the external environment can interrupt the normal activity of systems vital for health and wellbeing independent of cognition.
Dissecting The Central Organisation Of Cough Neural Networks
Funder
National Health and Medical Research Council
Funding Amount
$880,928.00
Summary
Cough is the most prevalent symptom of lung disease and the most common reason for people to seek medical advice. However, cough neural processes are poorly defined and as a result current cough therapies are largely ineffective making cough a significant unmet clinical problem. This project will novel viral strategies to dissect and manipulate cough neural pathways in the brain, providing insights into the neural processing of airway sensations and coughing.
Vasomotor Ganglionic Transmission: The Preganglionic Peptide And The Second Gear
Funder
National Health and Medical Research Council
Funding Amount
$451,896.00
Summary
Blood pressure depends on nerve signals that travel from the central nervous system to blood vessels. In the middle of this pathway is a relay station - the sympathetic ganglion cell. Transmission through this relay station has recently been shown to have not only a fixed but also a variable component - the 'second gear'. The project tests if and how three likely candidate peptide molecules, one in the nerves, two in the bloodstream, control this 'second gear' and hence regulate blood pressure.
A novel sensory neural circuit has been identified innervating the airways and lungs. The anatomical organisation of this circuit has been described to some extent in previous studies, however there is a significant gap in knowledge with respect to its functional importance. This project will develop methods to address this knowledge gap and in doing so the project will firstly describe how this circuit controls breathing under normal conditions and secondly how this becomes dysregulated during
FUNCTIONAL IMAGING OF THE BRAINSTEM AND CORTICAL SITES OF BLOOD PRESSURE CONTROL IN HUMAN SUBJECTS IN HEALTH AND DISEASE
Funder
National Health and Medical Research Council
Funding Amount
$398,498.00
Summary
Disturbances in cardiovascular control underpin many diseases yet little is known about how the brain controls the heart and blood vessels. This project uses brain imaging (fMRI) and concurrent nerve recording in awake human subjects to increase our understanding of how normal blood pressure is maintained and how different disease states influence this control.
Reduced Baroreceptor Reflex Control Of Heart Rate In Chronic Renal Failure
Funder
National Health and Medical Research Council
Funding Amount
$490,288.00
Summary
People with kidney disease are more likely to die of heart disease than their ailing kidneys. One reason is because their hearts do not respond properly to changes in blood pressure, as the nerve circuits controlling the heart become dysfunctional. We will examine where and why components of this circuit are unable to respond to changes in blood pressure. This will help guide new treatments to reduce the incidence of heart disease and risk of death associated with kidney disease.
Network Interactions Between Cardiovascular Control Neurons In The Brainstem Underlie Sympathetic Tone
Funder
National Health and Medical Research Council
Funding Amount
$268,328.00
Summary
High blood pressure is a very significant risk factor for many common cardiovascular diseases. Blood pressure is normally tightly regulated by groups of neurons in the brainstem; although we know that this part of the brain becomes dysfunctional in patients with high blood pressure, we do not understand why. We have recently discovered that cardiovascular control neurons can influence each other. The project will determine the effect of such communication in the control of blood pressure.
Towards early detection of upper airway obstruction in children: investigation of autonomic control. This project focuses on the investigation of new indicators for early detection of upper airway obstruction (UAO)-which is a common sleep disorder in children. Failure to treat UAO can result in serious adverse outcomes including failure to thrive, neurocognitive deficits, developmental delay, behavioural disorders and cardiovascular disease. Thus, early treatment of UAO will significantly improv ....Towards early detection of upper airway obstruction in children: investigation of autonomic control. This project focuses on the investigation of new indicators for early detection of upper airway obstruction (UAO)-which is a common sleep disorder in children. Failure to treat UAO can result in serious adverse outcomes including failure to thrive, neurocognitive deficits, developmental delay, behavioural disorders and cardiovascular disease. Thus, early treatment of UAO will significantly improve quality of life for the child. Direct benefits to community health via reduced costs for medical treatment will also be a key outcome. The establishment of new diagnostic indicators will form the basis of new tools for identifying child sleep disorders and contribute to advancing Australia's international leading position in health technology. Read moreRead less