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
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
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
Hypertension (high blood pressure) is the commonest chronic condition in western societies, and can lead to strokes, heart attacks and kidney failure. In a disease known as primary aldosteronism (PAL), hypertension results from the excessive production of the salt-retaining hormone, aldosterone, by the the body's adrenal glands. In some patients, this is due to the growth of an aldosterone-producing adrenal tumour. Recent work performed within the Hypertension Unit at Greenslopes Hospital and co ....Hypertension (high blood pressure) is the commonest chronic condition in western societies, and can lead to strokes, heart attacks and kidney failure. In a disease known as primary aldosteronism (PAL), hypertension results from the excessive production of the salt-retaining hormone, aldosterone, by the the body's adrenal glands. In some patients, this is due to the growth of an aldosterone-producing adrenal tumour. Recent work performed within the Hypertension Unit at Greenslopes Hospital and continued by these investigators within the Hypertension Unit at Princess Alexandra Hospital has shown that PAL is the commonest potentially curable form of hypertension, accounting for at least 5% and possibly 10% of patients. Several lines of evidence accumulated by these investigators, including the detection of a new familial variety of PAL (Familial Hyperaldosteronism Type II or FH-II), suggest that PAL is a genetic disorder. The study sets out to locate the genetic defect causing PAL by comparing genetic material collected from affected members of these families with that from non-affected members, and by comparing genes from patients with PAL with those of unrelated, unaffected individuals. Once the genetics of this condition is understood, affected persons can be detected early in life, and even at birth, and the ill-effects of their developing conditions prevented.Read moreRead less
Improved Gene Therapy Strategies For Primary Pulmonary Hypertension
Funder
National Health and Medical Research Council
Funding Amount
$370,517.00
Summary
Many people develop problems with the blood vessels in the lungs, which then leads to a narrowing of these vessels and consequently a back-pressure strain on the heart. These disorders can arise from inherited diseases of the blood vessels themselves, or from accquired lung disease (for example due to smoking or chronic infections). At present there are few treatments which have any benefits for these patients and many must undergo lung or heart-lung transplantation. This project is desigened bo ....Many people develop problems with the blood vessels in the lungs, which then leads to a narrowing of these vessels and consequently a back-pressure strain on the heart. These disorders can arise from inherited diseases of the blood vessels themselves, or from accquired lung disease (for example due to smoking or chronic infections). At present there are few treatments which have any benefits for these patients and many must undergo lung or heart-lung transplantation. This project is desigened both to find out new information about the disease process that affects the lung blood vessels and to offer a strategy for new treatments. The project will use a crippled form of the cold virus to deliver genes to the lining of the lung blood vessels, then see what impact that has on the pressure within the vessels and the ways in which they respond to certain stresses. These studies will be carried out using laboratory animals. If successful, it may be possible to eventually design such viruses to deliver genes which have a helpful therapeutic impact on the disease in patients.Read moreRead less
HYPE: Hypertension And Preeclampsia After Non-steroidal Use For Post-partum Pain Relief; A Prospective, Stratified, Randomised Placebo-controlled Trial
Funder
National Health and Medical Research Council
Funding Amount
$174,504.00
Summary
After caesarean delivery of a baby most women will require analgesia. Traditionally anti-inflammatory medications (eg.diclofenac) have been given. Evidence exists that this medicine may increase the mother�s blood pressure. This can result in a longer hospital stay, blood pressure medications and exposure to the risks of high blood pressure (eg.stroke and increased bleeding). This study examines the effect of diclofenac on the mother�s blood pressure, analgesia and investigates the mechanisms be ....After caesarean delivery of a baby most women will require analgesia. Traditionally anti-inflammatory medications (eg.diclofenac) have been given. Evidence exists that this medicine may increase the mother�s blood pressure. This can result in a longer hospital stay, blood pressure medications and exposure to the risks of high blood pressure (eg.stroke and increased bleeding). This study examines the effect of diclofenac on the mother�s blood pressure, analgesia and investigates the mechanisms behind the increased blood pressure.Read moreRead less
Hypertension Induced By Prenatal Glucocorticoid Exposure: Roles Of Cerebral And Renal Renin-angiotensin Systems
Funder
National Health and Medical Research Council
Funding Amount
$497,500.00
Summary
High blood pressure is a major public health problem in Australia and other developed countries as it is a common risk factor for stroke, heart failure and kidney damage. At present, there is a great interest in the possibility that high blood pressure in adults can result from stresses experienced by the fetus before birth. However, it is not known how prenatal compromise could lead to high blood pressure. We have recently established an animal model (using sheep) in which brief exposure to glu ....High blood pressure is a major public health problem in Australia and other developed countries as it is a common risk factor for stroke, heart failure and kidney damage. At present, there is a great interest in the possibility that high blood pressure in adults can result from stresses experienced by the fetus before birth. However, it is not known how prenatal compromise could lead to high blood pressure. We have recently established an animal model (using sheep) in which brief exposure to glucocorticoids - known as stress hormones - administered to the mother during early gestation results in high blood pressure in the offspring in adulthood. Increased levels of these hormones could occur in women at times when many may be unaware of their pregnancy (ie. smoking marijuana, chronic insomnia, accidents, loss of loved one, physical or mental stress or abuse). In addition, high doses of synthetic glucocorticoids might be given to pregnant patients for the treatment of asthma and acute migraine. The early origins of hypertension are of considerable importance to a large section of the community, namely the 25% who develop hypertension at the age 45 or over. If even a small proportion of hypertension can be prevented by reducing fetal exposure to excess glucocorticoids the impact on cardiovascular illness may be large. This research proposal has the potential to explain the basis for at least some of the 'essential' hypertension for which a mechanism has not been discovered after decades of research. This project will examine the separate roles of the kidney and brain, and in particular will determine whether permanent changes can be induced by exposure to stress hormones during early fetal life. Knowledge gained from this project could be used in devising strategies aimed at preventing or treating high blood pressure in adults.Read moreRead less
Drugs that block the mineralocorticoid receptor (MR), which responds to adrenal hormones, protect against heart disease and hypertension. We have shown that this effect is in part due to MR blockade in inflammatory cells. This novel finding is being explored further to understand the precise role of the MR in inflammatory cells in normal physiology and in disease. An understanding of the role of the MR in different tissues will enable development of tissue specific treatments for heart disease.