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
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
Modulating the molecular and cellular physiology of ageing skeletal muscle. Understanding the underlying mechanisms of how ageing affects muscle is of increasing importance to the community as the number of older persons in the population continues to escalate and the age of retirement increases. Old muscles are slower and weaker than young muscles, and are more easily injured. This proposal is focussed on developing safe therapies to prevent or reverse these age-related effects. Making old musc ....Modulating the molecular and cellular physiology of ageing skeletal muscle. Understanding the underlying mechanisms of how ageing affects muscle is of increasing importance to the community as the number of older persons in the population continues to escalate and the age of retirement increases. Old muscles are slower and weaker than young muscles, and are more easily injured. This proposal is focussed on developing safe therapies to prevent or reverse these age-related effects. Making old muscles young again, is a research strategy that will promote healthy ageing and enable older Australians to enjoy a better quality of life.Read moreRead less
Examining the links between obesity and insulin resistance. Obesity prevalence is rapidly increasing in Australia and contributes to the onset of many chronic diseases, such as diabetes, heart disease and cancer. This project will examine how obesity contributes to disease risk and how modifying nutrient delivery and other interventions that protect from cellular stress reduces these risks.
Estrogen signalling in gonadotropes. Estrogen action is a normal prerequisite for cyclic function of reproduction in the female, but little is known about how this important hormone acts in the relevant cells of the pituitary gland (gonadotropes). In order to gain information on normal function, we will conduct studies on gonadotropes treated with estrogen in a range of paradigms. The information will be valuable in understanding normal reproduction, but will also form the basis of further studi ....Estrogen signalling in gonadotropes. Estrogen action is a normal prerequisite for cyclic function of reproduction in the female, but little is known about how this important hormone acts in the relevant cells of the pituitary gland (gonadotropes). In order to gain information on normal function, we will conduct studies on gonadotropes treated with estrogen in a range of paradigms. The information will be valuable in understanding normal reproduction, but will also form the basis of further studies to investigate the effects of drugs that affect estrogen action and environmental estrogens. Read moreRead less
Regenerating lizard tails: A model for understanding the process of lymphangiogenesis. In humans, impaired lymphatic drainage in limbs causes the debilitating swelling termed lymphoedema. Lymphoedema affects 500,000,000 people worldwide. In the developed world lymphoedema predominantly results from surgery for cancer, and occurs in approximately 25% of breast cancer patients. We will examine lymph vessel regeneration (lymphangiogenesis) in a naturally regenerating, complex structure (the lizard ....Regenerating lizard tails: A model for understanding the process of lymphangiogenesis. In humans, impaired lymphatic drainage in limbs causes the debilitating swelling termed lymphoedema. Lymphoedema affects 500,000,000 people worldwide. In the developed world lymphoedema predominantly results from surgery for cancer, and occurs in approximately 25% of breast cancer patients. We will examine lymph vessel regeneration (lymphangiogenesis) in a naturally regenerating, complex structure (the lizard tail), to describe the regrowth process and determine the abundance, location, functional properties and molecular control of the new lymphatics. Furthermore, if reptilian lymphatic growth factors can promote lymphangiogenesis in mammals, we can design novel therapeutic approaches using reptilian ligands to promote lymphangiogenesis in lymphoedematous human tissues.Read moreRead less
Unified framework of intestinal motility. The project aims to establish how a few fundamental mechanisms determine the large repertoire of intestinal motor patterns responsible for moving nutrients along the digestive tract. The project will combine experimental and theoretical data, with biomechanical and electrophysiological models to create a new understanding of this essential function of the body.
Electrophysiological and Anatomical Characterization of the Coronary Sinus Musculature and its Relationship to the Atria. This series of experiments will characterise the normal coronary sinus musculature and its connectivity to the atria of the heart and establish their electrical relationships. The underlying characteristics of the muscular connections will also be evaluated with a view to possible future manipulations of the system. Understanding normal heart impulse propagation is paramount ....Electrophysiological and Anatomical Characterization of the Coronary Sinus Musculature and its Relationship to the Atria. This series of experiments will characterise the normal coronary sinus musculature and its connectivity to the atria of the heart and establish their electrical relationships. The underlying characteristics of the muscular connections will also be evaluated with a view to possible future manipulations of the system. Understanding normal heart impulse propagation is paramount before we can understand and develop treatments for dealing with heart problems. This information will facilitate the development of techniques to treat and prevent heart rhythm disorders that are a common cause of morbidity in the community.Read moreRead less
Does muscle contribute to the maintenance of vitamin D status in winter? This project aims to test the mechanism by which vitamin D status is maintained in winter when input is low. The long half-life in blood of the vitamin D metabolite, 25-hydroxyvitamin D [25(OH)D], maintains an adequate vitamin D status over winter, when sunlight, which produces vitamin D in skin, is reduced. From preliminary data in sheep and mice, this project proposes that skeletal muscle, not fat, stores vitamin D. This ....Does muscle contribute to the maintenance of vitamin D status in winter? This project aims to test the mechanism by which vitamin D status is maintained in winter when input is low. The long half-life in blood of the vitamin D metabolite, 25-hydroxyvitamin D [25(OH)D], maintains an adequate vitamin D status over winter, when sunlight, which produces vitamin D in skin, is reduced. From preliminary data in sheep and mice, this project proposes that skeletal muscle, not fat, stores vitamin D. This project will test this hypothesis in sheep, cultured muscle cells and in transgenic mice. The project will confirm whether the processes identified in skeletal muscle contribute to the maintenance of vitamin D status, and identify ways of enhancing this process.Read moreRead less
Urinary continence and incontinence in men: New insight through new technologies. Healthy ageing in men is largely overlooked. Disorders of continence are surprisingly common with increasing age, and are socially debilitating. To understand changes in continence and address healthy ageing it is first necessary to gain an understanding of continence mechanisms in healthy men. Continence in women has received wide attention, but anatomy and function differ, as do the challenges throughout life (ch ....Urinary continence and incontinence in men: New insight through new technologies. Healthy ageing in men is largely overlooked. Disorders of continence are surprisingly common with increasing age, and are socially debilitating. To understand changes in continence and address healthy ageing it is first necessary to gain an understanding of continence mechanisms in healthy men. Continence in women has received wide attention, but anatomy and function differ, as do the challenges throughout life (childbirth vs. prostate disease). Using novel methods we will test a new hypothesis of male continence with the goal to provide new physiological discoveries, new methods, and baseline data upon which strategies to enhance healthy ageing and reduce the economic burden of disorders of continence can be developed and refined. Read moreRead less