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.
Neural Versus Humoral Activation Of The Sympathetic Nervous System In Renal Disease
Funder
National Health and Medical Research Council
Funding Amount
$293,567.00
Summary
In the healthy body, the kidney and the sympathetic nervous system work together to keep our blood pressure in the normal range, both in the short and long term. When people have kidney disease, this system fails and people can develop high blood pressure. High blood pressure can lead to heart attack and stroke, and so is a serious complication for people who already have kidney disease. It has previously been believed that major factors in this process are fluid retention and a circulating horm ....In the healthy body, the kidney and the sympathetic nervous system work together to keep our blood pressure in the normal range, both in the short and long term. When people have kidney disease, this system fails and people can develop high blood pressure. High blood pressure can lead to heart attack and stroke, and so is a serious complication for people who already have kidney disease. It has previously been believed that major factors in this process are fluid retention and a circulating hormone called angiotensin II, but we believe that the sympathetic nervous system is also very important. Further, we believe that sensory nerves in the kidney tell the brain something is wrong in the kidney, making the sympathetic nervous system increase blood pressure inappropriately. We will examine the relative role of the sensory nerves and the hormone angiotensin II in driving the sympathetic nervous system to increase blood pressure, using three different rat models of kidney disease. One of these models is a new rat model of polycystic kidney disease, which is the fourth most important cause of renal disease in Australia. We want to determine what parts of the brain are important in the pathway, and will also test treatments that block the two different pathways (nerves vs. hormones) to see what is the most effective way of controlling not only blood pressure but also slowing down the progression of kidney and heart disease. This work is important as it will not only help us understand how the brain and kidney communicate with each other, but will also have the potential to improve quality of treatment for people with kidney diseaseRead moreRead less
Cardiovascular Effects Of Enhanced Leptin Signalling
Funder
National Health and Medical Research Council
Funding Amount
$1,200,972.00
Summary
Leptin treatment causes weight loss, but leptin also increases blood pressure. We wish to determine if increasing leptin signalling, by modifying signal transduction pathways within leptin sensitive cells in the brain, can reduce weight without increasing blood pressure.
Understanding The Origins Of Neurogenic Hypertension
Funder
National Health and Medical Research Council
Funding Amount
$668,914.00
Summary
Brain cells that control the cardiovascular system are thought to have stopped dividing by adulthood. We recently discovered that this is not the case. Our initial findings suggest that these nascent cells might be important for maintaining normal blood pressure. This work will allow us to elucidate the function of these nascent cells and how they integrate into the circuit that controls the cardiovascular system. Our findings will be fundamental for understanding diseases such as hypertension.
Understanding Factors Involved In The Development Of Hypertension
Funder
National Health and Medical Research Council
Funding Amount
$757,492.00
Summary
High blood pressure is a major cause of cardiovascular diseases. Currently intervention occurs after the cardiovascular system is damaged. Our interest is in the development of high blood pressure, to determine whether early intervention could stop its progression. We identified that excitation of the sympathetic nervous system by the circuits that control breathing is important. We seek to further understand this interaction to identify novel approaches to treat high blood pressure.
Vasomotor Ganglionic Transmission: The Preganglionic Peptide And The Second Gear
Funder
National Health and Medical Research Council
Funding Amount
$451,896.00
Summary
Blood pressure depends on nerve signals that travel from the central nervous system to blood vessels. In the middle of this pathway is a relay station - the sympathetic ganglion cell. Transmission through this relay station has recently been shown to have not only a fixed but also a variable component - the 'second gear'. The project tests if and how three likely candidate peptide molecules, one in the nerves, two in the bloodstream, control this 'second gear' and hence regulate blood pressure.
Role Of The Medial Amygdala In Developing Neurogenic Hypertension
Funder
National Health and Medical Research Council
Funding Amount
$302,123.00
Summary
We aim to investigate the underlying mechanisms and pathways that regulate the activity of neurons located in the medial amgydala during stress that contribute long term to the development of hypertension. This study is highly relevant to people who inappropriately respond to typical daily stressors and we aim to provide direction for developing specific therapies to interrupt the adverse cardiovascular consequences of chronic stress.
Investigation Of A Novel Sympathetic Vasomotor Pathway
Funder
National Health and Medical Research Council
Funding Amount
$354,586.00
Summary
Blood pressure is regulated by sympathetic nerves to the heart and blood vessels, and it is believed that overactive sympathetic nerves contribute to many cases of hypertension. Overactive sympathetic nerves also contribute to, and worsen the disease process, in heart failure as well as other cardiovascular diseases. The regulation of sympathetic nerves is thus central to the understanding and treatment of cardiovascular disorders. The present proposal is specifically relevant to the hypertensio ....Blood pressure is regulated by sympathetic nerves to the heart and blood vessels, and it is believed that overactive sympathetic nerves contribute to many cases of hypertension. Overactive sympathetic nerves also contribute to, and worsen the disease process, in heart failure as well as other cardiovascular diseases. The regulation of sympathetic nerves is thus central to the understanding and treatment of cardiovascular disorders. The present proposal is specifically relevant to the hypertension which accompanies airway obstruction during sleep (obstructive sleep apnoea - OSA). We plan to study a novel class of sympathetic nerves ('accessory' sympathetic nerves), which are likely to be centrally involved in the hypertension of OSA, and probably also other conditions where sympathetic nerve activity is pathologically raised. 'Accessory' sympathetic nerves can cause a long-lasting amplification of the activity in the 'regular' sympathetic nerve pathway, enhancing its actions on the heart and blood vessels. The brain pathways that drive 'accessory' sympathetic nerves are essentially unknown. We seek to find out those pathways, study how they amplify the activity in the 'regular' pathway and explore their significance in an animal model of OSA. The outcomes of this study will be first, essential basic knowledge of a novel, but probably important, mechanism whereby the brain controls the cardiovascular system in health and disease. Second, the relevance of that mechanism to a specific type of neurogenic hypertension will have been defined.Read moreRead less
I am a medically trained physiologist studying how the brain controls the delivery of oxygen to the body, the removal of carbon dioxide and the maintenance of normal acid level in the blood. This branch of physiology is well known to anyone who has studied 'ABC' in a first aid programme. My work concerns the coordination of the breathing and blood pressure centres in the brain. It is crucial in the understanding of diseases such as obstructive sleep apnoea and hypertension.
How Does The Central Respiratory Generator Amplify Sympathetic Activity In Hypertension?
Funder
National Health and Medical Research Council
Funding Amount
$290,113.00
Summary
High blood pressure causes many life-threatening cardiovascular diseases, including heart failure and stroke. The cause of most high blood pressure is not known. Using an animal model of high blood pressure we have shown that an interaction, in the brain, between the nerve pathways that generate respiratory activity and regulate blood pressure is altered. This occurs early in life and our evidence strongly suggests this may be a cause of high blood pressure.