Sympathetic Nervous System Contribution To Hypertension : CNS Pathways, Neurotransmitters And Neuroeffector Mechanisms
Funder
National Health and Medical Research Council
Funding Amount
$450,750.00
Summary
High blood pressure (hypertension) 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 lifestyle, 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 d ....High blood pressure (hypertension) 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 lifestyle, 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. We need to understand why this occurs. One possibility is that renin (a chemical 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 contributes to high blood pressure. It does this indirectly by producing another hormone called angiotensin. Our research has shown that in conditions where the kidney releases excess of the hormone renin, which may occur if the blood supply to the kidney is reduced, a change occurs in the way in which the nervous system affects blood pressure. The nervous system is activated to increase the release of renin from the kidney. The effect of this is to make blood pressure increase further in what can become a vicious circle. At present it is not understood why and how this change occurrs. The major thrust of this project is to determine the mechanims by which the renal hormones signal the central nervous system to change the nature of the nervous activity back to the kidney. We want to know what parts of the brain are involved, how the nature of the activity in the nerves changes and also how the nervous control of the kidney changes (i.e. how the kidney changes its responsivness to the nerve activity). Because similar processes probably occur in nearly all forms of high blood pressure, our results will greatly improve our understanding of how this dangerous condition develops.Read moreRead less
Pain associated with bone cancer, fractures, osteoporosis, osteoarthritis, osteomyelitis (and other bone infections) often presents the clinician with a difficult problem of treatment as the pain can be debilitating and intractable. Most current treatments for bone pain are based on the assumption that the neural mechanisms underlying pain from different sources, whether it be visceral, cutaneous, muscular or bony, are the same, and can therefore be targeted with similar therapies. However, litt ....Pain associated with bone cancer, fractures, osteoporosis, osteoarthritis, osteomyelitis (and other bone infections) often presents the clinician with a difficult problem of treatment as the pain can be debilitating and intractable. Most current treatments for bone pain are based on the assumption that the neural mechanisms underlying pain from different sources, whether it be visceral, cutaneous, muscular or bony, are the same, and can therefore be targeted with similar therapies. However, little is known of the response properties, structure and organization of receptors and neurones responding to, and relaying information about painful stimuli, from bone to the brain. The objectives of this project are to reveal the fundamental neural mechanisms that account for the perception of bone pain. The project will test a series of specific hypotheses in order to explain why bone pain is often poorly controlled by standard pharmacological or surgical approaches. It is expected that this study will reveal the neural mechanisms responsible for relaying sensory information, in particular, that regarding painful stimuli, from bone to the brain. It will lead to a better understanding of the mechanisms of bone pain and form the template for future studies of its treatment.Read moreRead less
I am a physiologist working to understand how disturbances during pregnancy can alter fetal development and increase the risk of developing adult onset diseases such as cardiovascular disease, renal disease and diabetes. In particular I am interested in how alterations in kidney development may play a crucial role in disease development.
Mechanisms Responsible For Hypertension Caused By Perinatal Omega-3 Fatty Acid Deficiency
Funder
National Health and Medical Research Council
Funding Amount
$280,650.00
Summary
Does the nourishment we receive as babies, or even before birth, affect our adult health? The recent findings from Barker, Meaney, Langley-Evans and their co-workers, has established that intra-uterine and early post-natal factors, particularly nutrition, influence adult neural development and cardiovascular function. It appears that the dietary intake of omega-3 fatty acids in early life may be a critical factor in the development of hypertension. We reported (Nature Medicine 2001, 7: 258-259) ....Does the nourishment we receive as babies, or even before birth, affect our adult health? The recent findings from Barker, Meaney, Langley-Evans and their co-workers, has established that intra-uterine and early post-natal factors, particularly nutrition, influence adult neural development and cardiovascular function. It appears that the dietary intake of omega-3 fatty acids in early life may be a critical factor in the development of hypertension. We reported (Nature Medicine 2001, 7: 258-259) for the first time that the essential omega-3 fatty acid, alpha-linolenic acid (ALA), supplied in the early developmental period, affects blood pressure later in life. The work showed that moderate omega-3 fatty acid deficiency in the perinatal period resulted in hypertension, despite reversal of the deficiency at a time months before the assessment of blood pressure. These findings are suggestive of a critical period, during which time the development of normal blood pressure control mechanisms appears, at least partially, dependent upon the supply of omega-3 fatty acids. These findings suggest that omega-3 deficiency early in life may affect fatty acid metabolism, transport or uptake systems, such that re-feeding of the nutrients is functionally ineffective. Alternatively, deficiency of omega-3 fatty acids early in life may arrest development of one or more of the key signalling pathways in the control of blood pressure, such as the Brain Angiotensin System. The influence of dietary omega-3 fatty acid supply, relative to the critical period, on expression of genes involved in the control of blood pressure as well as in fatty acid metabolism, will be defined. Also, the role of the brain angiotensin system in omega-3 fatty acid deficiency-induced hypertension will be determined. We expect that the results of this study will profoundly affect hypertension research, as well as nutrition, particularly that for infants.Read moreRead less
Age-Related Changes In Body Composition And Fuel Metabolism: The Role Of Glucocorticoid Signalling In Osteoblasts
Funder
National Health and Medical Research Council
Funding Amount
$820,528.00
Summary
Our previous studies suggest that age related changes in fat tissue could be due to an increased level of glucocorticoids within bone forming cells (osteoblasts). Mice in which the level of glucocorticoids in osteoblasts is selectively decreased were no different from normal mice at a young age but with ageing were protected against development of obesity and diabetes. This project will examine how bone influences age related changes in fat mass and examine ways in which this might be prevented.
Exploring Neurological Complications In Animal Models Of Metabolic Disease
Funder
National Health and Medical Research Council
Funding Amount
$337,432.00
Summary
Diabetes causes ongoing damage to the central and peripheral nervous systems. Our research aims to understand the mechanisms of nervous system damage in diabetes by investigating changes in nervous system function overtime in animal models of pre-diabetes, type 2 diabetes and type 1 diabetes. This study specifically aims to utilize indices that can be correlated with measures obtainable in human studies and thereby achieve results with strong clinical relevance and potential for translation.
Study Of The Functional Consequences Of Angiotensin II Induced Increases In Renal Innervation
Funder
National Health and Medical Research Council
Funding Amount
$393,750.00
Summary
Hypertension (high blood pressure) is a major public health problem in Australia, being a key risk factor for cardiovascular diseases such as heart attack and stroke. More ominously, recent WHO reports show that cardiovascular disease is the major health burden facing developing countries, particularly in our region. Although some of the burden of cardiovascular diseases may be reduced by effective public health measures (e.g., to reduce saturated fat intake), hypertension remains largely imperv ....Hypertension (high blood pressure) is a major public health problem in Australia, being a key risk factor for cardiovascular diseases such as heart attack and stroke. More ominously, recent WHO reports show that cardiovascular disease is the major health burden facing developing countries, particularly in our region. Although some of the burden of cardiovascular diseases may be reduced by effective public health measures (e.g., to reduce saturated fat intake), hypertension remains largely impervious to preventative public health measures. While treatment of established high blood pressure can reduce the incidence of cardiovascular disease, preventing the development of hypertension in the first place is not possible at this time. A major impediment to the development of effective public health measure is our lack of knowledge of the pathological mechanisms involved, despite over 100 years of active research effort. The experiments planned in this study will probe below the surface of two important facts known about hypertension but not previously brought together - that the kidney's blood vessels and nerves are remodeled in hypertension, and that the kidney's control of the level of blood pressure must be changed in order for high blood pressure to develop in the first place. We hope that pursuit of this experimental line of enquiry will provide new clues on where to look for initiating factors in human hypertension.Read moreRead less