This project aims to discover the nervous pathways and mechanisms in the brain that control body temperature. We hope to identify the nerve cells in the brain that detect increases in the core temperature of the body and determine the nervous pathways that project from them to increase blood flow to the skin when we become hot. This research may lead to a better understanding of heat exhaustion which is especially dangerous to the elderly.
Brain Angiotensin: Generation, Localisation And Physiological Function
Funder
National Health and Medical Research Council
Funding Amount
$209,250.00
Summary
The renin angiotensin system is one of the major homonal systems of the body that regulate the cardiovascular system and bodily salt and water balance. Drugs that inhibit the function of this system by reducing the blood level of the hormone angiotensin II or blocking the receptors at which it acts are in the forefront of treatment of high blood pressure and heart failure. It has been proposed that a separate brain renin angiotensin system exists that is not influenced by angiotensin II in the b ....The renin angiotensin system is one of the major homonal systems of the body that regulate the cardiovascular system and bodily salt and water balance. Drugs that inhibit the function of this system by reducing the blood level of the hormone angiotensin II or blocking the receptors at which it acts are in the forefront of treatment of high blood pressure and heart failure. It has been proposed that a separate brain renin angiotensin system exists that is not influenced by angiotensin II in the blood stream because of the blood-brain barrier. Strains of mice in which the genes that code for two components of this system - angiotensin converting enzyme (the enzyme responsible for generating angiotensin II) and angiotensinogen (the protein which gives rise to angiotensin II) provide excellent tools to elucidate this system in the brain. By studying these mice we will be able to determine whether angiotensin converting enzyme is necessary in the brain for foreming angiotensin II, and we will be able to determine the sites in the brain where authentic angiotensin peptides exist. We will also determine whether angiotensin II transmits information between neurons in the brain that play a role in control of the cardiovascular system and body fluid balance.Read moreRead less
This proposal aims to examine central mechanisms important in stress related hypertension. My team will focus on the role of tissue plasminogen activator in mediating inhibitory effects of chronic stress on neural plasticity and examine inhibitory dysfunction in GABAergic and nitric oxide pathways that lead to increased sympathetic activity and elevated blood pressure. Importantly, we will investigate the potential of three interventions directed at each as therapies for hypertension.
Interactions Between RAGE And The Type 1 Angiotensin Receptor Determine The Pro-atherosclerotic Actions Of Angiotensin II
Funder
National Health and Medical Research Council
Funding Amount
$521,956.00
Summary
Heart attacks and strokes are a major cause of death and disability in Australians. Activation of the renin angiotensin system plays a key role in the development and progression of atherosclerosis, the process that leads to narrowing and obstruction of arteries. In preliminary data we have found a way to block these pathways without affecting the control of blood pressure. We believe that interventions based on these data will be important for the prevention and treatment of heart disease.
The Persisting Vascular Effects Of Activation Of The Renin-Angiotensin System
Funder
National Health and Medical Research Council
Funding Amount
$628,456.00
Summary
Heart attacks and strokes are the major cause of death and disability in Australians. Heart disease is widely viewed to be the legacy of our diet and lifestyle, and even that of our parents. We propose to explore in detail the molecular mechanism of how this imprinting comes about and identify new targets to prevent, retard or reverse heart disease.
Modulating Pathogenic Signalling Towards The Prevention Of Diabetic Complications
Funder
National Health and Medical Research Council
Funding Amount
$622,655.00
Summary
Diabetes is associated with an increased risk of heart attacks and kidney failure. There remains an urgent need for new targets and therapies for preventing, arresting, treating and reversing these diabetic complications. My research directly focuses on identifying and validating these targets treatments, building on strong preliminary data and understanding of the molecular mechanisms set off by high sugar levels.