Urotensin-II In Human Heart: Investigation Of Mechanisms Involved In Cardiac Function
Funder
National Health and Medical Research Council
Funding Amount
$255,990.00
Summary
The normal function of the body is maintained by naturally occurring compounds. Some for example affect the heart, fine tuning it to make it beat faster or slower, or beat with greater or less force when required in different situations in health and disease. We were the first to show just recently that a small protein which occurs naturally in the body, called urotensin-II can affect the way the heart beats. We showed that extremely tiny amounts increase the force of the heart beat. Our finding ....The normal function of the body is maintained by naturally occurring compounds. Some for example affect the heart, fine tuning it to make it beat faster or slower, or beat with greater or less force when required in different situations in health and disease. We were the first to show just recently that a small protein which occurs naturally in the body, called urotensin-II can affect the way the heart beats. We showed that extremely tiny amounts increase the force of the heart beat. Our findings indicate that urotensin-II is the most potent heart stimulator identified to date. In patients with heart failure, short term stimulation of heart contraction is beneficial, supplying the heart and other organs with vital oxygen and nutrients. However, in the long term excessive stimulation causes worsening of the patients condition. Very little is currently known about the way in which urotensin-II alters heart function. The goal of our study is to understand the mechanism involved in urotensin-II mediated effects on the heart. This will involve identifying the location of urotensin-II and its receptors in the heart, and determining what signalling changes occur after the interaction of urotensin-II with its receptors. Urotensin-II must first be cleaved from a larger drug. We will determine where in the heart this cleavage occurs and whether the process is crucial to the ability of urotensin-II to stimulate contraction of the heart. Since stimulators of heart contraction are detrimental to patients with heart failure in the long term, we will determine whether these patients have more urotensin-II in their blood than patients who do not have heart failure. If the levels of urotensin-II are higher in heart failure patients, it may indicate a need to interfere with the interaction of urotensin-II with its receptors.Read moreRead less
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
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.
A Type II Diabetes Adn Obesity Prevention Program For Primary School Aged Rural Indigenous Children
Funder
National Health and Medical Research Council
Funding Amount
$1,497,369.00
Summary
This project aims to develop and evaluate the impact of an innovative multi-component community and school-based program for type II diabetes and obesity prevention program for Indigenous and non-Indigenous rural children.