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
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.
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
Understanding The Origins Of Neurogenic Hypertension
Funder
National Health and Medical Research Council
Funding Amount
$668,914.00
Summary
Brain cells that control the cardiovascular system are thought to have stopped dividing by adulthood. We recently discovered that this is not the case. Our initial findings suggest that these nascent cells might be important for maintaining normal blood pressure. This work will allow us to elucidate the function of these nascent cells and how they integrate into the circuit that controls the cardiovascular system. Our findings will be fundamental for understanding diseases such as hypertension.
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.
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.
PACAP: The Mechanism Underlying Sleep Apnoea-induced Hypertension
Funder
National Health and Medical Research Council
Funding Amount
$505,117.00
Summary
10% of Australians suffer from sleep apnoea; a cause of high blood pressure. Untreated, high blood pressure causes heart failure, kidney failure and stroke. A major cause of high blood pressure is an increased amount of nerve activity that controls the heart and blood vessels. In this proposal we will investigate how a brain chemical, called PACAP, affects nerve activity and blood pressure in a model of sleep apnoea. This information may lead to new and better treatments for high 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.
Cell-selective Deletion Of Brain AT1A Receptors In Hypertension: Effect On Blood Pressure, Increased ROS Production And Inflammation.
Funder
National Health and Medical Research Council
Funding Amount
$578,268.00
Summary
Angiotensin is important for normal regulation of blood pressure but is also involved in cardiovascular diseases. Interruption of angiotensin’s actions is a common treatment of these diseases. Functional deletion of angiotensin receptors decreases blood pressure. Surprisingly the site(s) in the body responsible for this decrease are not known. We will examine the role of angiotensin receptors in the brain in the control of blood pressure in health and in cardiovascular disease.