ACE2, A New Regulator Of The Renin Angiotensin System
Funder
National Health and Medical Research Council
Funding Amount
$492,625.00
Summary
Angiotensin converting enzyme (ACE) is a key enzyme in the renin-angiotensin system (RAS), converting Angiotensin I to the potent vasoconstrictor Angiotensin II (Ang II). ACE inhibitors have been highly successful in the management of hypertension, are standard therapy following myocardial infarction to delay the development of heart failure, and also reduce the rate of progression of renal disease. Recently, a novel enzyme called ACE2 has been discovered in the heart and kidneys. Unlike ACE, AC ....Angiotensin converting enzyme (ACE) is a key enzyme in the renin-angiotensin system (RAS), converting Angiotensin I to the potent vasoconstrictor Angiotensin II (Ang II). ACE inhibitors have been highly successful in the management of hypertension, are standard therapy following myocardial infarction to delay the development of heart failure, and also reduce the rate of progression of renal disease. Recently, a novel enzyme called ACE2 has been discovered in the heart and kidneys. Unlike ACE, ACE2 causes the formation of the vasodilator, Ang 1-7. We have data in the heart and the kidney that supports the concept that ACE2 acts in a counter-regulatory manner to ACE. We suggest that ACE2 may play an important role to modulate the balance between vasoconstrictors and vasodilators in the heart and kidney. The studies detailed in this proposal are designed to specifically examine the role and regulation of ACE2 in the healthy heart and kidney as well as in cardiovascular and renal disease. The project brings together two groups with complementary skills and techniques, both of whom have collaborations with the discoverers of ACE2, and who have been exploring the role of ACE2 as evidenced from our recent publication (Tikellis et al, Hypertension in press, 2003).Read moreRead less
Brain Angiotensin: Generation, Localisation And Physiological Function
Funder
National Health and Medical Research Council
Funding Amount
$209,250.00
Summary
The renin angiotensin system is one of the major homonal systems of the body that regulate the cardiovascular system and bodily salt and water balance. Drugs that inhibit the function of this system by reducing the blood level of the hormone angiotensin II or blocking the receptors at which it acts are in the forefront of treatment of high blood pressure and heart failure. It has been proposed that a separate brain renin angiotensin system exists that is not influenced by angiotensin II in the b ....The renin angiotensin system is one of the major homonal systems of the body that regulate the cardiovascular system and bodily salt and water balance. Drugs that inhibit the function of this system by reducing the blood level of the hormone angiotensin II or blocking the receptors at which it acts are in the forefront of treatment of high blood pressure and heart failure. It has been proposed that a separate brain renin angiotensin system exists that is not influenced by angiotensin II in the blood stream because of the blood-brain barrier. Strains of mice in which the genes that code for two components of this system - angiotensin converting enzyme (the enzyme responsible for generating angiotensin II) and angiotensinogen (the protein which gives rise to angiotensin II) provide excellent tools to elucidate this system in the brain. By studying these mice we will be able to determine whether angiotensin converting enzyme is necessary in the brain for foreming angiotensin II, and we will be able to determine the sites in the brain where authentic angiotensin peptides exist. We will also determine whether angiotensin II transmits information between neurons in the brain that play a role in control of the cardiovascular system and body fluid balance.Read moreRead less
Regulation Of Endothelin Converting Enzyme Subcellular Distribution And Vascular Endothelin Production.
Funder
National Health and Medical Research Council
Funding Amount
$399,750.00
Summary
Endothelin is a hormone produced by the endothelial cells that line blood vessels. The role of this hormone is cause blood vessels to constrict (vasoconstriction), thus causing a rise in blood pressure. The synthesis of this hormone is crucially dependant on an enzyme that has to be located on the surface of the endothelial cell. The aim of this grant is to understqand the mechanisdms by which the location of this enzyme within the cell is regulated. The knowledge gained from this study will not ....Endothelin is a hormone produced by the endothelial cells that line blood vessels. The role of this hormone is cause blood vessels to constrict (vasoconstriction), thus causing a rise in blood pressure. The synthesis of this hormone is crucially dependant on an enzyme that has to be located on the surface of the endothelial cell. The aim of this grant is to understqand the mechanisdms by which the location of this enzyme within the cell is regulated. The knowledge gained from this study will not only help us better understand the mechanism of endothelin production but it may also offer an insight into future therapeutic startegies to prevent the formation of endothelin, thus preventing vasoconstriction.Read moreRead less
Novel Vasoactive Pathways In Liver Disease; Experimental And Clinical Studies
Funder
National Health and Medical Research Council
Funding Amount
$535,333.00
Summary
Cirrhosis of the liver due to chronic hepatitis and other common liver diseases is now a major cause of illness and death in Australia. This project will examine how a hormone system called the renin angiotensin system contributes to the development of liver damage in these diseases. We will study whether drugs targeting this system can be used to reduce liver scarring and prevent the development of cirrhosis and its complications.