I am a cardiovascular physiologist investigating the origin of the large increases in cardiac and renal sympathetic nerve activity in heart failure,the causes of acute renal failure in septic shock and mechanisms to reduce myocardial ischaemia-reperfusion
Role Of Urotensin II, A Novel Vasoconstrictor Factor, In Cardiovascular Disease
Funder
National Health and Medical Research Council
Funding Amount
$196,018.00
Summary
Urotensin II (UII) is a newly discovered peptide that may play an important role in human health and disease. It has been found to be a potent constrictor (narrower) of blood vessels and therefore may be involved in diseases such as hypertension (high blood pressure) and heart failure (weak heart muscle disease). Furthermore, many other factors that constrict blood vessels have also been found to have effects on key organs, such as the heart. Our preliminary data suggests that this is also true ....Urotensin II (UII) is a newly discovered peptide that may play an important role in human health and disease. It has been found to be a potent constrictor (narrower) of blood vessels and therefore may be involved in diseases such as hypertension (high blood pressure) and heart failure (weak heart muscle disease). Furthermore, many other factors that constrict blood vessels have also been found to have effects on key organs, such as the heart. Our preliminary data suggests that this is also true of urotensin II. The proposal studies seek to determine the role of urotensin II in the : (i) periphery, by assessing contraction of forearm vessels to low doses of UII in normal volunteer subjects and patients with hypertension and heart failure; (ii) heart, by measuring expression of UII and its receptor in normal and failing human heart tissue; the UII response to experimental heart attack in the rat and in cell culture of important heart cells; (iii) general circulation, by measuring plasma levels in health and disease. The significance of this project is that if it is found that UII plays an important role in these diseases, then agents that block this system may represent a major therapeutic advance in the management of these diseases.Read moreRead less
Study Of The Functional Consequences Of Angiotensin II Induced Increases In Renal Innervation
Funder
National Health and Medical Research Council
Funding Amount
$393,750.00
Summary
Hypertension (high blood pressure) is a major public health problem in Australia, being a key risk factor for cardiovascular diseases such as heart attack and stroke. More ominously, recent WHO reports show that cardiovascular disease is the major health burden facing developing countries, particularly in our region. Although some of the burden of cardiovascular diseases may be reduced by effective public health measures (e.g., to reduce saturated fat intake), hypertension remains largely imperv ....Hypertension (high blood pressure) is a major public health problem in Australia, being a key risk factor for cardiovascular diseases such as heart attack and stroke. More ominously, recent WHO reports show that cardiovascular disease is the major health burden facing developing countries, particularly in our region. Although some of the burden of cardiovascular diseases may be reduced by effective public health measures (e.g., to reduce saturated fat intake), hypertension remains largely impervious to preventative public health measures. While treatment of established high blood pressure can reduce the incidence of cardiovascular disease, preventing the development of hypertension in the first place is not possible at this time. A major impediment to the development of effective public health measure is our lack of knowledge of the pathological mechanisms involved, despite over 100 years of active research effort. The experiments planned in this study will probe below the surface of two important facts known about hypertension but not previously brought together - that the kidney's blood vessels and nerves are remodeled in hypertension, and that the kidney's control of the level of blood pressure must be changed in order for high blood pressure to develop in the first place. We hope that pursuit of this experimental line of enquiry will provide new clues on where to look for initiating factors in human hypertension.Read moreRead less
Interactions Between RAGE And The Type 1 Angiotensin Receptor Determine The Pro-atherosclerotic Actions Of Angiotensin II
Funder
National Health and Medical Research Council
Funding Amount
$521,956.00
Summary
Heart attacks and strokes are a major cause of death and disability in Australians. Activation of the renin angiotensin system plays a key role in the development and progression of atherosclerosis, the process that leads to narrowing and obstruction of arteries. In preliminary data we have found a way to block these pathways without affecting the control of blood pressure. We believe that interventions based on these data will be important for the prevention and treatment of heart disease.
Insulin Regulated Aminopeptidase: A New Cardiovascular Target
Funder
National Health and Medical Research Council
Funding Amount
$672,650.00
Summary
Cardiovascular disease, leading to heart attack or stroke is the largest cause of death in Australia. We have evidence that inhibition of a newly described enzyme (IRAP) by angiotensin IV is protective in a model of atherosclerosis. Excitingly we have preliminary data indicating that mice deficient in IRAP have better vascular function therefore we will further investigate this as well as the effectiveness of newly developed IRAP inhibitors in preventing development of cardiovascular disease.
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.