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
Thioredoxin Interacting Protein: A Novel Regulator Of Angiogenesis And Impaired Neovascularisation In Diabetes Mellitus
Funder
National Health and Medical Research Council
Funding Amount
$292,639.00
Summary
Heart disease is the leading cause of death and treatment options such as bypass surgery are unsuitable for many sufferers, particularly those with diabetes. This project investigates the regulation of new blood vessel growth through the action of antioxidants and also examines the contribution of adult stem cells to this process. Regulating new blood vessel growth provides a novel means to overcome current problems in the management of both non-diabetic and diabetic patients with heart disease.
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
Regulation Of Mesenchymal Stem Cell Paracrine Activity In Post-myocardial Infarction Cardiac Repair
Funder
National Health and Medical Research Council
Funding Amount
$73,212.00
Summary
Heart failure remains to be a major cause of morbidity in Australian population. After myocardial infarction, the damaged heart undergoes a series of compensatory adjustments to maintain the workload, termed cardiac remodeling. The resultant beneficial response in the short term eventually becomes deleterious. Using adult stem cells, the project aims to develop a better treatment to manipulate the progression of such responses and prevent hearts from entering the end stage heart failure.
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.
Macrophage Migration Inhibitory Factor (MIF): Pathological And Therapeutic Significance In Post- Infarct Inflammation
Funder
National Health and Medical Research Council
Funding Amount
$547,577.00
Summary
Ischemic heart injury mediated by the inflammatory response has a significant impact on the prognosis. MIF is a central factor mediating and amplifying the inflammatory response but its role in heart disease remains largely untested. This project will study, for the first time, the crucial role of MIF in ischemic heart disease and will establish important experimental evidence for developing new anti-inflammation therapeutic strategies against ischemic heart injury.
Regulation Of Endothelin Converting Enzyme Subcellular Distribution And Vascular Endothelin Production.
Funder
National Health and Medical Research Council
Funding Amount
$399,750.00
Summary
Endothelin is a hormone produced by the endothelial cells that line blood vessels. The role of this hormone is cause blood vessels to constrict (vasoconstriction), thus causing a rise in blood pressure. The synthesis of this hormone is crucially dependant on an enzyme that has to be located on the surface of the endothelial cell. The aim of this grant is to understqand the mechanisdms by which the location of this enzyme within the cell is regulated. The knowledge gained from this study will not ....Endothelin is a hormone produced by the endothelial cells that line blood vessels. The role of this hormone is cause blood vessels to constrict (vasoconstriction), thus causing a rise in blood pressure. The synthesis of this hormone is crucially dependant on an enzyme that has to be located on the surface of the endothelial cell. The aim of this grant is to understqand the mechanisdms by which the location of this enzyme within the cell is regulated. The knowledge gained from this study will not only help us better understand the mechanism of endothelin production but it may also offer an insight into future therapeutic startegies to prevent the formation of endothelin, thus preventing vasoconstriction.Read moreRead less