Understanding Local And Regional Determinants Of EDHF And NO Dysfunction In Resistance Arteries In Diabetes
Funder
National Health and Medical Research Council
Funding Amount
$771,295.00
Summary
Diabetes is a serious and increasing health burden worldwide. Most of the sickness and death associated is due to complications arising in the blood vessels. The inner lining of blood vessels in small arteries uses several different mechanisms to ensure proper blood flow, and in diabetes these are impaired. This study will reveal the cellular mechanisms involved and identify pathways for therapeutic intervention to alleviate the debilitating effects of small artery disease.
TARGETING ROS-INDUCED DAMAGE RESCUES THE DIABETIC HEART
Funder
National Health and Medical Research Council
Funding Amount
$487,669.00
Summary
Over 1 million Australians have diabetes. Many of these patients die from cardiovascular disease. We have identified free radicals as a major cause of decreased pumping function and impaired recovery from each heartbeat in the diabetic heart. Stronger antioxidant approaches and-or activation of protective protein pathways is a more effective treatment for reversing impaired function in the diabetic heart, preventing or delaying heart failure in patients with diabetes.
Non-neuronal ATP: Regulation Of Release And Action In The Bladder
Funder
National Health and Medical Research Council
Funding Amount
$451,553.00
Summary
Incontinence disorders are costly and debilitating. How the bladder signals the normal sensation of fullness as well as the urgent need to void urine (urgency) is still not fully understood. The signaling molecule ATP is released during bladder stretch. Using animal and human bladder, we will study how the bladder lining is involved in this signaling process, by measuring how bladder chemicals interact with stretch to modulate ATP release, and how ATP can influence nerve impulses to the brain.
The normal functioning of many organs is controlled by several types of nerves through releasing chemicals called neurotransmitters. A new type of nerve has been identified recently; these are called nitrergic nerves. They release a nitric oxide-like transmitter to control the relaxation of smooth muscle. Although it is known that nitrergic nerves play important roles in the regulation of functions of various organs, the nature of its transmitter has not been elucidated. Our recent study suggest ....The normal functioning of many organs is controlled by several types of nerves through releasing chemicals called neurotransmitters. A new type of nerve has been identified recently; these are called nitrergic nerves. They release a nitric oxide-like transmitter to control the relaxation of smooth muscle. Although it is known that nitrergic nerves play important roles in the regulation of functions of various organs, the nature of its transmitter has not been elucidated. Our recent study suggests that the nitrergic transmitter is more close to a redox form of nitric oxide such as nitroxyl anion than to nitric oxide itself. This project will investigate further the mechanism of nitrergic transmission including the nature of the nitrergic transmitter. The proposed research will help to answer important questions regarding the mechanisms of nitrergic transmission and thus may throw additional light to the nature of the nitrergic transmitter. The findings may also be significant for the development of new drugs (such as new NO donors) which interact with nitrergic mechanisms.Read moreRead less
Aberrant Oligosaccharide Processing Of Nox2-oxidase As A Mechanism Of Vascular Oxidative Stress In Atherosclerosis
Funder
National Health and Medical Research Council
Funding Amount
$552,565.00
Summary
Excessive production of free radicals by an enzyme called Nox2 may be a cause of artery disease leading to heart attacks and strokes. This study will identify whether the addition of sugarchains to Nox2 causes it to be expressed at the surface of cells allowing the free radicals it produces to exit the cell and cause damage to the blood vessel wall. Charaterising this new pathway of excessive free radical production may pave the way for new diagnostics and treatments for artery disease.
Mechanisms Of Action Of Neurochemicals And Modulators In Human Intestine: Changes In Disease
Funder
National Health and Medical Research Council
Funding Amount
$442,500.00
Summary
Inflammatory bowel disease (IBD) and idiopathic chronic constipation (ICC) are two serious gastrointestinal disorders, for which no effective medical treatment is known. We will investigate the hypothesis that abnormalities in the nerve chemicals found in the gut contribute to the aetiology of these diseases. Our studies will examine the sites of action (receptors) for these chemicals (neurotensin and acetylcholine) in the small and large intestine. The mechanisms governing motility changes in r ....Inflammatory bowel disease (IBD) and idiopathic chronic constipation (ICC) are two serious gastrointestinal disorders, for which no effective medical treatment is known. We will investigate the hypothesis that abnormalities in the nerve chemicals found in the gut contribute to the aetiology of these diseases. Our studies will examine the sites of action (receptors) for these chemicals (neurotensin and acetylcholine) in the small and large intestine. The mechanisms governing motility changes in response to these chemicals have been well studied in animal intestine, but there is little detailed information from the human intestine. This study will provide insight into the mechanisms operating in the normal bowel, providing a base for comparing bowel obtained from patients with IBD or ICC. We will also study bowel removed at surgery for acute diverticular disease (DD), representing another type of inflammation. Studies on isolated segments of colon from ICC patients will determine whether the contractility of the muscle is abnormal in general or only with respect to the chemicals under investigation. Other studies will investigate the inflammatory processes occurring in the bowel and whether this differs in IBD. Our work will facilitate understanding of the function of the bowel in health and in gastrointestinal disorders and may lead to new medical treatments for IBD and ICC.Read moreRead less
Targeting Arginase In Peripheral Arterial Occlusive Disease
Funder
National Health and Medical Research Council
Funding Amount
$243,945.00
Summary
Peripheral artery occlusive disease causes narrowing of large peripheral blood vessels which can result in severe pain, gangrene and stroke. Its prevalence is steadily increasing in western countries. This proposal aims to characterize the role of an enzyme (arginase) in PAOD and determine whether it may be a new drug target for treatment of this disease.
NOVEL CGMP-BASED THERAPIES PREVENT LEFT VENTRICULAR REMODELLING
Funder
National Health and Medical Research Council
Funding Amount
$533,433.00
Summary
Over 300,000 Australians are affected by heart failure. Current drugs for cardiac remodelling (the decline in heart pumping function and changed structure that precede heart failure) slow but not reverse disease progression. We have identified a new, nitrovasodilator-based therapy superior to those currently available. We propose it represents a more effective treatment for reversing abnormalities in both structure and function in the remodelled heart, preventing or delaying heart failure.
The Role Of Connexins In Blood Pressure Regulation: Use Of A Conditional Gene Expression System
Funder
National Health and Medical Research Council
Funding Amount
$583,767.00
Summary
Cell coupling through gap junctions is said to play an important role in regulating blood flow and blood pressure. However data obtained from mice, in which specific gap junctions are deleted, may be compromised by compensatory changes in other junctions. We have validated a new method for rapidly and reversibly altering gap junctions in adult mice with oral sugar. This technique will enable us to directly determine whether interference with cell coupling affects blood flow and blood pressure.