Myoendothelial Gap Junctions: Their Composition And Role In Vasodilator Responses Attributed To EDHF
Funder
National Health and Medical Research Council
Funding Amount
$282,750.00
Summary
Cardiovascular disease, including coronary heart disease and stroke, continues to be the major cause of death in Australia and hypertension is a significant risk factor. The endothelium, which lines blood vessels of all sizes, is critical to the control of blood flow to the organs of the body. Endothelial cells release factors which can cause blood vessels to constrict or to relax, thus decreasing or increasing blood flow, respectively. Under normal conditions, the endothelium is more important ....Cardiovascular disease, including coronary heart disease and stroke, continues to be the major cause of death in Australia and hypertension is a significant risk factor. The endothelium, which lines blood vessels of all sizes, is critical to the control of blood flow to the organs of the body. Endothelial cells release factors which can cause blood vessels to constrict or to relax, thus decreasing or increasing blood flow, respectively. Under normal conditions, the endothelium is more important as a source of relaxing factors, while under hypertensive conditions, the balance is shifted in favour of the release of constricting factors. Thus, restoration of the vasodilatory function of the endothelium is seen as an important new therapeutic target in the treatment of vascular disorders. Present data suggests that the action of one of the major endothelial derived vasodilatory factors, the so-called endothelium-derived hyperpolarizing factor, EDHF, requires the presence of particular structures within the vascular wall, but little is known about the molecules of which they are comprised. We have identified two unique situations, during development and during hypertension, when these structures are present in vessels in which they are absent in normal adults. We will use gene microarrays to identify the specific molecules involved in these structures and use physiological studies to test the role of these proteins and structures in vasodilatory responses. The results of these studies may identify new targets for therapeutic intervention to restore the action of EDHF in hypertension.Read moreRead less
Salt And Cardiovascular Disease: Does Acute Salt-Sensitivity Convey Greater Cardiovascular Risk?
Funder
National Health and Medical Research Council
Funding Amount
$597,578.00
Summary
Salt intake of Australian adults is 10X more than required. Further, salt intake in very young children is alarmingly high secondary to high consumption of salty snacks and processed food. High dietary salt intake has been associated with increased cardiovascular disease and death. We will examine the cardiovascular risks for adults and children on a high salt diet and examine whether switching to a low salt diet ameliorates the high blood pressure and heart disease caused by high salt diets
Role Of AMP-activated Protein Kinase In Salt Excretion And Hypertension
Funder
National Health and Medical Research Council
Funding Amount
$133,351.00
Summary
High blood pressure is a significant health problem and may result from the kidneys not being able to get rid of salt properly. The mechanisms underlying this are unclear. I will investigate the role of a kidney protein, called AMPK, in salt excretion in mice. I will also look at the effects that diabetes and obesity have on the function of this protein. The overall aim is to improve the understanding of what causes high blood pressure which will ultimately aid the development of new treatments ....High blood pressure is a significant health problem and may result from the kidneys not being able to get rid of salt properly. The mechanisms underlying this are unclear. I will investigate the role of a kidney protein, called AMPK, in salt excretion in mice. I will also look at the effects that diabetes and obesity have on the function of this protein. The overall aim is to improve the understanding of what causes high blood pressure which will ultimately aid the development of new treatments for it.Read moreRead less
FUNCTIONAL IDENTIFICATION OF CORTICAL AND SUBCORTICAL SITES RESPONSIBLE FOR NEUROGENIC HYPERTENSION IN HUMANS
Funder
National Health and Medical Research Council
Funding Amount
$514,644.00
Summary
Blood pressure is normally maintained at a relatively constant level through reflexes involving the brainstem, but we have recently shown that higher areas of the brain are also involved in the regulation of blood pressure in humans. Here, we will use the novel methodologies we have developed to study functional and structural changes in the brain in patients with essential and renovascular hypertension.
Hypothalamic Regulation Of Cardiovascular Function In Hypertension And Stress
Funder
National Health and Medical Research Council
Funding Amount
$570,880.00
Summary
Blood pressure is controlled to a large extent by nerves, known as sympathetic nerves, that supply the heart and blood vessels. The activity of sympathetic nerves is commonly increased in people with high blood pressure, particularly younger patients. This has the effect of constricting blood vessels and increasing heart rate, which places an additional load on the heart, and increasing the risk of heart attacks and stroke. Sympathetic nerves are also activated strongly in response to stress. In ....Blood pressure is controlled to a large extent by nerves, known as sympathetic nerves, that supply the heart and blood vessels. The activity of sympathetic nerves is commonly increased in people with high blood pressure, particularly younger patients. This has the effect of constricting blood vessels and increasing heart rate, which places an additional load on the heart, and increasing the risk of heart attacks and stroke. Sympathetic nerves are also activated strongly in response to stress. In some people stress can trigger an extreme reaction, called a panic disorder, characterised by intense sympathetic activation, which also increases the risk of heart attacks. A region in the brain called the hypothalamus plays a key role in generating these increases in sympathetic nerve activity. This project aims first to identify the precise region or regions in the hypothalamus that are responsible for causing increased sympathetic activity in high blood pressure, and also in response to acute stress. There is also evidence from studies in humans that drugs which act on a particular type of receptor in the brain (called a serotonin receptor) can strongly inhibit the normal response to stress. We also aim to determine exactly where and how such drugs work. These studies may lead to much more effective treatments for high blood pressure and stress-related disorders.Read moreRead less
Understanding The Molecular Heterogeneity Of Response And Resistance To Anti-HER2-ErbB2 Agents In Breast Cancer
Funder
National Health and Medical Research Council
Funding Amount
$373,173.00
Summary
A revolution in cancer care will take place in the next decade as we aim to individualize treatment for each patient. A subtype of breast cancer relies on a growth factor called HER2 for growth. Treatments that block HER2 are highly effective and have less side effects than chemotherapy. My study aims to further understand of the biology of this subtype of breast cancer and action of anti-HER2 agents as this will allow us to treat this aggressive type of breast cancer more effectively.