Role Of The Hypothalamus, Oxidative Stress And Angiotensin In Chronic Stress
Funder
National Health and Medical Research Council
Funding Amount
$535,333.00
Summary
Stress can trigger life threatening cardiovascular events and its impact is much greater when blood pressure is raised. We seek to determine which chemical type of brain neuron and which region is responsible for amplifying the responses to repeated stress in an animal model that closely resembles the human form of the disease. We will focus specifically on the hypothalamus which controls the sympathetic nervous system.
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
Does Pregnancy Cause Morphological Changes In Central As Well As Peripheral Nerve Pathways That Control Blood Pressure?
Funder
National Health and Medical Research Council
Funding Amount
$382,538.00
Summary
Pregnancy changes blood pressure but the mechanism is unknown. We will use state-of-the-art anatomical methods to define how pregnancy alters nerves controlling blood pressure. We will identify changes in the information the nerve cells receive, in their shape and in the way they communicate with other blood pressure-controlling nerve cells. This information will help to develop new ways to prevent and treat pre-eclampsia, a major cause of death and disability for mothers and their newborns.
Neurogenic Hypertension In The Spontaneously Hypertensive Mouse : Role Of The Hypothalamic-brainstem Sympathetic Axis
Funder
National Health and Medical Research Council
Funding Amount
$475,917.00
Summary
In human high blood pressure, particularly in the young, an overactive nervous system is thought to be a major underlying cause. Using a unique mouse model of high blood pressure which closely resembles this aspect of the human disease, we will examine which brain cells and neuro- chemicals are involved, particularly in a small area that is involved in regulating the hormonal and nervous system response to stress. From this we hope to be able to target these chemicals with specific therapy.
Cardiovascular Reactivity To Stress: Role Of Redox Signalling In The Hypothalamus And Brainstem
Funder
National Health and Medical Research Council
Funding Amount
$606,979.00
Summary
Cardiovascular disease is Australia's greatest health problem. It kills more people than any other disease and affected 3.5 million Australians in 2004-05. More and more evidence suggests a relationship between the risk of cardiovascular disease and mental stress. But more research is needed on how stress contributes to heart disease risk. This project aims to determine the role of harmful molecules, called free oxygen radicals, in brain in mediating effects of stress on cardiovascular system.
Influence Of Superoxide On The Central Cardiovascular Response To Emotional Stress: Cellular And Subcellular Mechanisms
Funder
National Health and Medical Research Council
Funding Amount
$642,599.00
Summary
Cardiovascular disease is Australia's greatest health problem. It kills more people than any other disease and affected 3.5 million Australians in 2004-05. More and more evidence suggests a relationship between the risk of cardiovascular disease and mental stress. But more research is needed on how stress contributes to heart disease risk. This project aims to determine the role of harmful molecules, called free oxygen radicals, in brain in mediating effects of stress on cardiovascular system.
Central Regulation Of Blood Pressure : Role Of Angiotensin And Nitric Oxide
Funder
National Health and Medical Research Council
Funding Amount
$488,250.00
Summary
High blood pressure 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 lifestyles, 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 s ....High blood pressure 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 lifestyles, 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. A major question has been to understand why this occurs. One possibility is angiotensin (a hormone 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 contribute to high blood pressure. Our research has shown that normally brain angiotensin has relatively little activity but can be switched on by specific situations such as stress or a high salt. This may be by depleting anti-oxidants and producing an oxidative stress in the brain. With aging, stress, lack of exercise and other various environmental influences our body is less able to cope with oxidative stress which is the result of the normal cells function. The major thrust of this project is to determine whether the long term contribution of angiotensin in the brain to high blood pressure is caused by a high level of oxidative stress in the brain. We will see whether experimental animals still develop high blood pressure if angiotensin is blocked in the brain and see whether changing the oxidative stress levels in the brain affects this role. We will be able to better understand the interplay between these molecules in the brain which opens the way for the development of new highly specific drugs that can prevent the high level of nerve activity to the heart and kidney and hence the development of high blood pressure.Read moreRead less