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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
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
The long-term side effects of renal denervation are unknown. This project is designed to (1) investigate the potential atherosclerosis-promoting effect of renal denervation, and (2) to study the effectiveness of anti-inflammatory drugs to minimize this potential side effect. Ultimately, this project may improve the beneficial effects and minimize the potential side effects of renal denervation by routinely treating renal denervated patients with anti-inflammatory drugs.
Renal AT2R Are A Therapeutic Target For The Treatment Of Hypertension In Women
Funder
National Health and Medical Research Council
Funding Amount
$605,939.00
Summary
Being female is associated with better renal function, resistenace to renal injury and hypertension, but it is not understood why. Our work demonstrates that women have more angiotensin type 2 receptors (AT2R) in the kidney then men. In men AT2R have been suggested to protect against hypertension and renal damage. We predict that the effects of AT2R stimulation will be greater in women and therefore the protective benefits greater.
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.
An abnormal blood pressure (BP) response to a clinical exercise stress test is a signal for increased cardiovascular disease risk. However, current clinical guidelines do not provide evidence based information surrounding values that may constitute this increased risk. The EXERcise stress Test collaboratION (EXERTION) aims to fill this knowledge gap via establishment of a large, national database of exercise stress test results, linked to acute and chronic cardiovascular disease outcomes.
Cardiac Fibrosis In Hypertensive Heart Disease: Cellular And Molecular Mechanism
Funder
National Health and Medical Research Council
Funding Amount
$631,979.00
Summary
Cardiac fibrosis due to excess collagen accumulation in the heart is a major cause of heart failure associated with high blood pressure and greatly increases the risk of sudden death. At present there are no effective therapies to prevent cardiac fibrosis. Understanding how fibrosis develops and identifying the cells and factors responsible will lead to development of novel therapies for cardiac fibrosis.
Novel Soluble Guanylate Cyclase Activators For Pulmonary Artery Hypertension
Funder
National Health and Medical Research Council
Funding Amount
$474,087.00
Summary
Pulmonary hypertension (elevated blood pressure in the lungs) is a life-threatening condition with few treatment options. We have recently identified a new class of drug that may improve blood vessel function in the lungs and thereby provide a new drug for the management of this group of patients.