Genes Encoding The Epithelial Sodium Channel Subunits And Blood Pressure
Funder
National Health and Medical Research Council
Funding Amount
$429,330.00
Summary
High blood pressure is a prominent risk factor for heart attack and stroke which kill over 30,000 Australians each year. Blood pressure is determined by the combination of inherited predisposition and lifestyle factors such as diet. Understanding these combinations offers new opportunities for preventing or treating high blood pressure and reducing the incidence of cardiovascular disease. As part of an NHMRC-funded project, we have discovered recently that genes controlling the amount of salt ex ....High blood pressure is a prominent risk factor for heart attack and stroke which kill over 30,000 Australians each year. Blood pressure is determined by the combination of inherited predisposition and lifestyle factors such as diet. Understanding these combinations offers new opportunities for preventing or treating high blood pressure and reducing the incidence of cardiovascular disease. As part of an NHMRC-funded project, we have discovered recently that genes controlling the amount of salt excreted by the kidneys appear to be linked with high blood pressure. If confirmed, this observation might provide an explanation of salt on blood pressure in susceptible individuals. Building on our basic observation, we shall extend our studies to place the findings beyond reasonable doubt. We shall investigate the gene sequences to discover what changes might lead to high blood pressure and examine how these affect the kidney and body salt. These studies combine forces of two large international blood pressure research groups. Our observation is the first internationally to define a blood pressure gene in the general community. Our results are potentially relevant to many more people than only those with very high blood pressure.Read moreRead less
Physiological Function Of Nedd4-2 In Regulating The Epithelial Sodium Channel And Cystic Fibrosis Transmembrane Conductance Regulator
Funder
National Health and Medical Research Council
Funding Amount
$949,572.00
Summary
Optimal transport of sodium and chloride ions is essential for the maintenance of electrolyte balance, blood volume, blood pressure and lung function. We are studying the control of a key sodium channel (the epithelial sodium channel) and a key chloride channel (cystic fibrosis transmembrane conductance regulator) by an enzyme called Nedd4-2. This project will enable us to understand how Nedd4-2 regulates these two ion channels and to study the pathological consequences of the loss of Nedd4-2.
The Role Of Peroxisome Proliferator Activated Receptor Gamma In Sodium Transport In Human Proximal Tubule Cells
Funder
National Health and Medical Research Council
Funding Amount
$566,946.00
Summary
Renal failure accounts for a considerable component of the excess morbidity and mortality observed in patients with diabetes mellitus. In addition, the emotional, social and cost to the community of dialysis is enormous. PPARgamma is activated by drugs that have been recently introduced for the treatment of type 2 diabetes mellitus. The propensity for these drugs to cause fluid retention has emerged recently as the most common serious adverse drug reaction associated with these compounds. the de ....Renal failure accounts for a considerable component of the excess morbidity and mortality observed in patients with diabetes mellitus. In addition, the emotional, social and cost to the community of dialysis is enormous. PPARgamma is activated by drugs that have been recently introduced for the treatment of type 2 diabetes mellitus. The propensity for these drugs to cause fluid retention has emerged recently as the most common serious adverse drug reaction associated with these compounds. the definitive cause of fluid retention with the use of PPAR gamma agonists is not known. Studies reported in the last 12 - 18 months have suggested that a common pathway may be involved in the development of the fluid retention, the high blood pressure and the scarring that occurs in the kidney. This project will be the first to provide a comprehensive examination of the effect of PPARgamma induction on renal sodium absorption and fluid retention in the human proximal tubule cells and the potential molecular mechanisms underlying them. This will provide insight as to potential adjuvant treatments for patients with diabetes.Read moreRead less
Open-label Randomised Trial Of Tolvaptan Versus Fluid Restriction In Hospitalised Patients With Moderate-severe Hyponatraemia
Funder
National Health and Medical Research Council
Funding Amount
$132,743.00
Summary
Low blood sodium level, known as hyponatraemia, is the most common electrolyte problem. It occurs in 15% of hospital patients, and can cause confusion, seizure and fatal brain swelling. Standard treatment for hyponatraemia is limiting oral fluid, but this is slow and not always effective. The drug tolvaptan works in mild hyponatraemia, but hasn't been formally tested in severe cases. We will compare benefits and risks of tolvaptan versus fluid restriction in patients with severe hyponatremia.
Interactions Between H5N1 And The Respiratory Epithelium
Funder
National Health and Medical Research Council
Funding Amount
$623,065.00
Summary
This project examines the hypothesis that the severity of H5N1 infection is due to activation of signalling pathways in the lung not activated by human influenza and leads to fluid accumulation in the lungs death of respiratory cells. This study will improve our understanding of influenza infection and identify targets for treatment of H5N1.