How Spinal Afferent Nerves Cause Vasodilation Of Mesenteric Arteries
Funder
National Health and Medical Research Council
Funding Amount
$353,250.00
Summary
Healthy function of the gastrointestinal tract requires an adequate blood supply during periods of varying demand. Inadequate blood supply to the gut contributes to disorders ranging in severity from mild through to lethal. Reduced blood supply to the gut is a trigger for multiple organ failure syndrome; a leading cause of death in critically ill patients following major surgery, trauma or haemorrhage. It is believed that damage to the lining of the gut, during periods of reduced flow, trigger i ....Healthy function of the gastrointestinal tract requires an adequate blood supply during periods of varying demand. Inadequate blood supply to the gut contributes to disorders ranging in severity from mild through to lethal. Reduced blood supply to the gut is a trigger for multiple organ failure syndrome; a leading cause of death in critically ill patients following major surgery, trauma or haemorrhage. It is believed that damage to the lining of the gut, during periods of reduced flow, trigger inflammatory mechanisms throughout the body. Mesenteric ischaemia is a disorder which occurs as a chronic, non-occlusive form, or as acute episodes, which are often lethal, . Temporary increases in blood supply are also known to play a vital role in protecting the gut from acid, toxins and attack by pathogens. The major mechanism underlying increases in bloody supply is dilation of arterial vessels. This occurs focally, at the site of damage, via local mechanisms, but this is supplemented by a more widespread dilation of arteries upstream, mediated by branches of sensory neurones that innervate blood vessels directly. Currently, there is no information about how these sensory neurones are activated. This is crucial to understand how they work. We hypothesise that these sensory neurones are activated by chemical and mechanical stimuli in the gut wall, which make them release vasodilator chemicals onto the arteries upstream and thus amplify the local increases in blood flow. We will test this by recording from sensory nerves, identifying the ones which project to blood vessels and determine which chemicals and mechanical stimuli they are excited by. We will then fill them with dye, using a method that we have recently developed, to visualise their branching patterns both inside and outside the gut wall. In this way, we will understand how this powerful protective mechanism is activated at times of need, and how it may fail under some circumstances.Read moreRead less
Role For Zinc And ZIP2 In The Action Of Nitric Oxide And In Vascular Protection Against Cigarette Smoke And Cardiovascular Disease
Funder
National Health and Medical Research Council
Funding Amount
$685,941.00
Summary
The NO/cGMP signalling pathway, which is central to cardiovascular physiology and protection against disease, is only fully effective when there are adequate levels of zinc in the vascular endothelium. This is especially important where zinc stores are depleted (elderly, smokers, diabetics and kidney disease). There is an urgent clinical need to implement strategies to monitor vascular Zn status. This application will explore the underlying science and translate these to the clinic.
Novel Soluble Guanylate Cyclase Activators For Pulmonary Artery Hypertension
Funder
National Health and Medical Research Council
Funding Amount
$474,087.00
Summary
Pulmonary hypertension (elevated blood pressure in the lungs) is a life-threatening condition with few treatment options. We have recently identified a new class of drug that may improve blood vessel function in the lungs and thereby provide a new drug for the management of this group of patients.
Targeting Aldosterone Receptors In Cerebrovascular Disease
Funder
National Health and Medical Research Council
Funding Amount
$857,712.00
Summary
Stroke represents a major health (accounting for 6% of all deaths) and economic (costs Australia $2.14 billion per year) burden on society, thus clearly more effective treatments are needed. This project will investigate the role of two substances produced in the body – angiotensin II and aldosterone – in stroke outcome, and whether targeting their receptor(s) may prevent poor outcomes following stroke.
Exported Epoxide Hydrolases Of The Malaria Parasite, Plasmodium Falciparum, And Their Role In Modulation Of Host Vasoregulation
Funder
National Health and Medical Research Council
Funding Amount
$342,054.00
Summary
The major aim of this study is to define the physiological role of the parasite EHs, and to establish whether they modulate levels of EETs within infected erythrocytes. I will examine if infected erythrocytes have impaired vasoactive properties and also determine if this pathway has therapeutic potential
A New Target For Allergic Inflammation: The Sphingolipid Pathway
Funder
National Health and Medical Research Council
Funding Amount
$588,617.00
Summary
Collectively, allergic diseases contribute immensely to the burden of health care in Australia. Notably, allergic reactions are symptomatic responses to a normally innocuous environmental antigen. Allergic diseases include asthma, hay fever, food allergy, anaphylaxis, insect sting and drug allergy. This project aims to understand the underlying mechanisms associated with allergic reactions such that it may aid in the identification of novel targets for the development of new treatments.
The Role Of Angiotensin-(1-7), Angiotensin Converting Enzyme-2 And The Mas Receptor In Liver Fibrosis And The Development And Maintenance Of Portal Hypertension
Funder
National Health and Medical Research Council
Funding Amount
$55,575.00
Summary
Chronic liver disease is widespread in our community, and is increasing due to fatty liver disease and viral hepatitis. Liver disease leads to permanent liver scarring, liver cancer and other life-threatening complications. This research investigates the role of a hormone system called the renin-angiotensin system in liver disease, and investigated the use of drugs that act on this system for the prevention and treatment of liver scarring and these complications.