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
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.
Neural Versus Humoral Activation Of The Sympathetic Nervous System In Renal Disease
Funder
National Health and Medical Research Council
Funding Amount
$293,567.00
Summary
In the healthy body, the kidney and the sympathetic nervous system work together to keep our blood pressure in the normal range, both in the short and long term. When people have kidney disease, this system fails and people can develop high blood pressure. High blood pressure can lead to heart attack and stroke, and so is a serious complication for people who already have kidney disease. It has previously been believed that major factors in this process are fluid retention and a circulating horm ....In the healthy body, the kidney and the sympathetic nervous system work together to keep our blood pressure in the normal range, both in the short and long term. When people have kidney disease, this system fails and people can develop high blood pressure. High blood pressure can lead to heart attack and stroke, and so is a serious complication for people who already have kidney disease. It has previously been believed that major factors in this process are fluid retention and a circulating hormone called angiotensin II, but we believe that the sympathetic nervous system is also very important. Further, we believe that sensory nerves in the kidney tell the brain something is wrong in the kidney, making the sympathetic nervous system increase blood pressure inappropriately. We will examine the relative role of the sensory nerves and the hormone angiotensin II in driving the sympathetic nervous system to increase blood pressure, using three different rat models of kidney disease. One of these models is a new rat model of polycystic kidney disease, which is the fourth most important cause of renal disease in Australia. We want to determine what parts of the brain are important in the pathway, and will also test treatments that block the two different pathways (nerves vs. hormones) to see what is the most effective way of controlling not only blood pressure but also slowing down the progression of kidney and heart disease. This work is important as it will not only help us understand how the brain and kidney communicate with each other, but will also have the potential to improve quality of treatment for people with kidney diseaseRead moreRead less
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.
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.
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.