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Mechanisms Behind The Activation Of Cardiac And Renal Sympathetic Nerve Activity In Heart Failure
Funder
National Health and Medical Research Council
Funding Amount
$452,670.00
Summary
Heart failure is associated with an increase in messages from the brain that control how fast the heart beats but the factors involved remain poorly understood. This project will enable a better understanding ot the mechanisms controlling this increase in the activity of the nerves. This understanding will provide a new avenue for therapy and for the development of new treatments.
Control Of Sympathetic Nerves That Talk To The Immune System
Funder
National Health and Medical Research Council
Funding Amount
$385,958.00
Summary
The two complex systems of the body, the immune system and the nervous system, communicate with each other. This proposal studies one of the major pathways from brain to immune system - sympathetic immuno-efferent nerves. In stroke, these pathways cause profound immunosuppression, causing susceptibility to infection. Their poorly understood central and peripheral pathways will be defined and mapped by this study.
Sympathetic Nervous System Contribution To Hypertension : CNS Pathways, Neurotransmitters And Neuroeffector Mechanisms
Funder
National Health and Medical Research Council
Funding Amount
$450,750.00
Summary
High blood pressure (hypertension) is a major public health problem in Western society with approximately 20% of adults affected. If left untreated, serious damage to organs can occur and the risk of sudden cardiac death or stroke is greatly increased. While many factors contribute to the development of hypertension such as lifestyle, genes, diet, weight and exercise levels, a common feature in the early stages is an overactive nervous system in the kidney and in the heart which is most likely d ....High blood pressure (hypertension) is a major public health problem in Western society with approximately 20% of adults affected. If left untreated, serious damage to organs can occur and the risk of sudden cardiac death or stroke is greatly increased. While many factors contribute to the development of hypertension such as lifestyle, genes, diet, weight and exercise levels, a common feature in the early stages is an overactive nervous system in the kidney and in the heart which is most likely due to altered signals from the brain. We need to understand why this occurs. One possibility is that renin (a chemical released from the kidney) that is known to control body fluid, also acts in the brain to increase nerve activity to the kidney and heart and in this way contributes to high blood pressure. It does this indirectly by producing another hormone called angiotensin. Our research has shown that in conditions where the kidney releases excess of the hormone renin, which may occur if the blood supply to the kidney is reduced, a change occurs in the way in which the nervous system affects blood pressure. The nervous system is activated to increase the release of renin from the kidney. The effect of this is to make blood pressure increase further in what can become a vicious circle. At present it is not understood why and how this change occurrs. The major thrust of this project is to determine the mechanims by which the renal hormones signal the central nervous system to change the nature of the nervous activity back to the kidney. We want to know what parts of the brain are involved, how the nature of the activity in the nerves changes and also how the nervous control of the kidney changes (i.e. how the kidney changes its responsivness to the nerve activity). Because similar processes probably occur in nearly all forms of high blood pressure, our results will greatly improve our understanding of how this dangerous condition develops.Read moreRead less
A Neurogenic Basis Of Obesity Hypertension: Role Of Adipokines And Ghrelin In Regulating Sympathetic Vasomotor Activity
Funder
National Health and Medical Research Council
Funding Amount
$358,035.00
Summary
During the development of obesity, brain centres are inappropriately activated by factors such as leptin which are released by excess fat accumulation. This reults in high blood pressure. We seek to determine which chemical type of brain neuron is responsible for receiving these signals in a specific brain region in an animal model that closely resembles the human form of the disease. We will focus specifically on areas known to control the sympathetic nervous system.
IDENTIFICATION AND FUNCTION OF RECEPTORS ON SYMPATHETIC TERMINAL SCHWANN CELLS
Funder
National Health and Medical Research Council
Funding Amount
$235,500.00
Summary
The terminals of sympathetic nerves control many of the internal organs. Pharmacological intervention to promote or antagonize the effects of these terminals is very important in a number of different disease states of the autonomic nervous system. The present research proposal sets out to determine the way in which glial cells that partly envelop these terminals control their capacity to function.
Role Of The Medial Amygdala In Developing Neurogenic Hypertension
Funder
National Health and Medical Research Council
Funding Amount
$302,123.00
Summary
We aim to investigate the underlying mechanisms and pathways that regulate the activity of neurons located in the medial amgydala during stress that contribute long term to the development of hypertension. This study is highly relevant to people who inappropriately respond to typical daily stressors and we aim to provide direction for developing specific therapies to interrupt the adverse cardiovascular consequences of chronic stress.
Central Control Of Blood Pressure: Neurotransmitters, Receptors, Signal Transduction And Gene Expression
Funder
National Health and Medical Research Council
Funding Amount
$941,350.00
Summary
The way that the brain controls blood pressure is of crucial significance to our day-to-day survival. Nerves in the lower brain and spinal cord cause blood pressure to be maintained at appropriate levels for all types of daily activities ranging from sleep, when blood pressure is very low, to exercise when blood pressure can be very high. In hypertension, a disorder that afflicts around 10% of the community, blood pressure is elevated to an extent that damages organs such as the brain, heart, ki ....The way that the brain controls blood pressure is of crucial significance to our day-to-day survival. Nerves in the lower brain and spinal cord cause blood pressure to be maintained at appropriate levels for all types of daily activities ranging from sleep, when blood pressure is very low, to exercise when blood pressure can be very high. In hypertension, a disorder that afflicts around 10% of the community, blood pressure is elevated to an extent that damages organs such as the brain, heart, kidney and eye. It now appears that most cases of hypertension have as their basis a disorder of the way that the brain, through the sympathetic nervous system, controls the heart and blood vessels. Many different brain systems need to change the way that blood is distributed in the body at different times. For example, when we eat, blood goes preferentially to our gut; if we exercise, to our heart and muscles; if we are cold, to our skin and when we think, to our brain. This specialised regulation of blood flow is accomplished by the interaction of nerves in the lower brain and spinal cord. It involves a vast array of special chemical messengers acting on specific receptors through different intracellular mechanisms and involving the turning on or off of genes. Only a few of these neurotransmitter systems are well understood. At the core of our proposal, we aim to determine which neurotransmitters systems are important for which cardiovascular functions. We anticipate that this new information will permit the development of new approaches to the management of hypertension. The reason for this is that since different pathways use different messenger systems, it should become possible to tailor therapy to suit hypertension without causing undesirable side-effects.Read moreRead less
Targeting Prevention And Treatment Of Hypertensive Cardiovascular Disease
Funder
National Health and Medical Research Council
Funding Amount
$774,540.00
Summary
Hypertension, high blood pressure, is a major global health burden. It contributes to heart disease, stroke and kidney failure, and as such is a major cause of premature death worldwide. Advances in the treatment of hypertension has meant that more people are living with disabilities associated with cardiovascular disease. Our work focuses on identifying new treatments to prevent the devastating effects of hypertension on organ function to improve quality of life in men and women.
BRAIN IMAGING OF CARDIOVASCULAR CONTROL DURING MUSCLE PAIN
Funder
National Health and Medical Research Council
Funding Amount
$370,983.00
Summary
One in every five people in Australia suffers chronic pain and a third of these have severe pain associated with severe disability. The incapacitating effects of long-lasting pain are not just psychological, but affect many systems, including the cardiovascular system. We are interested in why pain causes blood pressure to increase in some people but not in others: patients with post-surgical chronic pain have nearly twice the prevalence of clinical hypertension than patients without pain.
Central Excitatory Pathways Of The Autonomic Nervous System
Funder
National Health and Medical Research Council
Funding Amount
$323,164.00
Summary
The central pathways of autonomic regulation are well known, but the functions of specific pathways in physiological settings remains an elusive goal. We will evaluate the role of two physiologically important autonomic pathways for sleep apnea and the circadian control of the body by genetically deleting the transmitter, glutamate, in transgenic mice. A greater understanding of these pathways is critical in unraveling autonomic nervous system function in health and disease.