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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.
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
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.
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
Inadequately controlled blood pressure remains the leading cause of death world wide despite the availability of numerous effective drugs. We have successfully pioneered a catheter-based approach using radiofrequency-energy to disrupt renal nerves and lower blood pressure in patients with resistance to conventional drug treatment. We now aim to test the role of this ground-breaking technology as a potential cure (blood pressure control without antihypertensive medication) for hypertension.
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.
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.
Protective Role Of The Depressor Arm Of The Renin-angiotensin System During Pregnancy
Funder
National Health and Medical Research Council
Funding Amount
$633,384.00
Summary
The motivation for unveiling the normal hormonal and molecular mechanisms involved in the extraordinary vasodilatation associated with pregnancy is that understanding these fundamental processes may provide novel insights into the pathophysiology of preeclampsia and intrauterine growth restriction, as well as potential therapeutic strategies for not only the treatment of these pregnancy specific conditions but also cardiovascular and renal diseases in non-pregnant women and men.