Roles Of The Peptide Hormone, Ghrelin, In The Spinal Cord
Funder
National Health and Medical Research Council
Funding Amount
$414,326.00
Summary
This study investigates the control of internal organs of the body, the heart, blood vessels, intestine and bladder. We have made the new and surprising discovery that ghrelin, previously known to be a hormone, is probably also a neurotransmitter in the spinal cord. This raises the possibility that drugs that act on ghrelin receptors in the spinal cord could be used to treat high blood pressure or other problems of internal organs.
Stress and obesity can lead to high blood pressure and greatly increase the risk of life threatening cardiovascular events. This application seeks to determine which chemicals and parts of the brain are responsible for amplifying the responses to repeated stress and during obesity in animal models leading to hypertension.
Ultrasonic Blood Pressure Measurement On Implanted Biomedical Surfaces
Funder
National Health and Medical Research Council
Funding Amount
$170,250.00
Summary
The project would develop a prototype device reporting blood pressure on a biomedical implant surface. The device would extract data in real time from a standard ultrasound scanner that images the implant. The School of Mathematical Sciences at Monash University will be contracted to develop this ultrasound pressure sensor.
Respiratory Modulation Of RVLM Premotor Neurons: Role In The Sympathetic Over-activity Of Hypertension.
Funder
National Health and Medical Research Council
Funding Amount
$338,605.00
Summary
Hypertension is a common health disorder in all societies and is a major risk factor for the development of life threatening cardiovascular diseases, including heart failure and stroke. Whilst some effective therapies are available, many patients are not adequately treated or have reduced quality of life due to serious side effects. There is a great need for alternative therapies. The central nervous system is clearly involved in hypertension although the level of that involvement is not well un ....Hypertension is a common health disorder in all societies and is a major risk factor for the development of life threatening cardiovascular diseases, including heart failure and stroke. Whilst some effective therapies are available, many patients are not adequately treated or have reduced quality of life due to serious side effects. There is a great need for alternative therapies. The central nervous system is clearly involved in hypertension although the level of that involvement is not well understood- i.e. is it a causal factor or just a contributor to the maintenance of established hypertension? The experiments outlined in this application are based on the observation that modulation of nervous activity to blood vessels is more influenced by the respiratory system in people with high blood pressure, than in normotensive people. We aim to test whether this increased respiratory modulation might be involved in the generation of the high blood pressure.Read moreRead less
How Does The Central Respiratory Generator Amplify Sympathetic Activity In Hypertension?
Funder
National Health and Medical Research Council
Funding Amount
$290,113.00
Summary
High blood pressure causes many life-threatening cardiovascular diseases, including heart failure and stroke. The cause of most high blood pressure is not known. Using an animal model of high blood pressure we have shown that an interaction, in the brain, between the nerve pathways that generate respiratory activity and regulate blood pressure is altered. This occurs early in life and our evidence strongly suggests this may be a cause of high blood pressure.
Sympathetic Control Of Cutaneous Blood Flow And Blood Pressure In Human Spinal Cord Injury
Funder
National Health and Medical Research Council
Funding Amount
$242,002.00
Summary
While spinal cord injury can cause devastating changes in the nervous system paralysis and loss of sensation relatively little is known about changes to the sympathetic nervous system. The sympathetic nervous system is intimately involved in the ongoing control of blood pressure, blood flow and temperature control. Loss of sympathetic control can occur following spinal cord injury. Interruption of descending pathways can result in partial or complete loss of sympathetic outflow from the thoracol ....While spinal cord injury can cause devastating changes in the nervous system paralysis and loss of sensation relatively little is known about changes to the sympathetic nervous system. The sympathetic nervous system is intimately involved in the ongoing control of blood pressure, blood flow and temperature control. Loss of sympathetic control can occur following spinal cord injury. Interruption of descending pathways can result in partial or complete loss of sympathetic outflow from the thoracolumbar segments. Complete decentralization can result in autonomic dysreflexia (autonomic hyperreflexia), in which sensory stimuli originating below the lesion evoke a reflex increase in sympathetic drive to the blood vessels, causing them to constrict. Because of this, blood pressure may rise suddenly and remain at such high levels that stroke and (occassionally) cardiac arrest may occur. This phenomenon, autonomic dysreflexia, is considered a medical emergency. The typical subjective signs of autonomic dysreflexia include a throbbing headache, tingling in the head or nasal congestion; sweating and flushing above the lesion are clinical signs that prompt medical staff to measure blood pressure and to locate the source of sensory irritation (usually a distended bladder or impacted colon, sometimes a pressure sore or ingrown toenail). Commonly, however, subclinical episodes go undetected, and this phenomenon of silent dysreflexia is of increasing concern. This project will develop means of assessing the integrity and state of the sympathetic nervous system below a lesion in patients with spinal cord injury and characterize the firing properties of reflexly activated sympathetic neurones.Read moreRead less
PREMOTOR SYMPATHETIC CONTROL OF BLOOD PRESSURE DURING PSYCHOLOGICAL STRESS: HYPOTHALAMUS VERSUS MEDULLA.
Funder
National Health and Medical Research Council
Funding Amount
$153,616.00
Summary
Health and well being depend in large part on a strong and efficient autonomic nervous system. The autonomic nervous system controls blood pressure, heart rate, gastrointestinal function, immune responses and certain forms of pain. Negative emotions can have a strong impact on autonomic function. We have all experienced the sweaty hands, pounding heart and intestinal discomfort when the mail arrives and bad news is expected or when we face a deadline for which we are not prepared. This is known ....Health and well being depend in large part on a strong and efficient autonomic nervous system. The autonomic nervous system controls blood pressure, heart rate, gastrointestinal function, immune responses and certain forms of pain. Negative emotions can have a strong impact on autonomic function. We have all experienced the sweaty hands, pounding heart and intestinal discomfort when the mail arrives and bad news is expected or when we face a deadline for which we are not prepared. This is known as psychological stress and it is usually associated with anxiety. Unfortunately, it is also the most common form of stress in modern urban life. There are clear indications that when these autonomic changes become chronic they can lead to hypertension, weak immune responses and gastric ulcers. In people already suffering from cardiovascular diseases they can also precipitate cardiac and cerebrovascular accidents. Clearly, the link between psychological stress and the autonomic nervous system needs to be explored in more detail. This project looks at the organization of the neural network in the brain and spinal cord that controls these responses. It uses a simple model of psychological stress in the conscious rat and recent non invasive techniques to record blood pressure and look at neuronal activity. We think that we have identified a group of neurons that may be controlling very specifically this response. It is located in the hypothalamus. The aim of this project is to further test the role of these neurons and find out what is controlling them. They will also be compared to another group of neurons that also controls blood pressure but apparently not in relation to psychological stress. The possibility that the cardiovascular response to psychological stress might be mediated by a specific group of neurons in the brain is a very exciting finding. It could lead to new therapeutic applications for acting against the short and long term effects of stress.Read moreRead less
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
Effects Of Ghrelin Receptor Ligands On Cardiovascular Function
Funder
National Health and Medical Research Council
Funding Amount
$516,207.00
Summary
Ghrelin is a hormone that is known to control food intake and growth hormone release. Our recent work shows that compounds that mimic ghrelin�s actions influence blood pressure by their effects in the brain, the spinal cord and on arteries. We will investigate the potential of such compounds to treat blood pressure disorders