Mechanisms Of Vascular Dysfunction During Acute And Chronic Hyperglycemia
Funder
National Health and Medical Research Council
Funding Amount
$56,700.00
Summary
Increased consumption of sugary drinks has contributed to an epidemic of obesity and diabetes and consequently cardiovascular disease. For the first time in living memory, this may well lead to declining life-expectancy. My research will examine both the short and long-term impact of sugary drinks on vital blood vessel function. In the process it will develop better methods to monitor blood vessel function and inform public health policy on sugary drinks and preventing cardiovascular disease.
The prevalence of liver cirrhosis worldwide is rising due. The majority of the morbidity and mortality, which arises with cirrhosis, occurs due to the development of portal hypertension. In cirrhosis unexplained vasodilatation of the splanchnic circulation occurs contributing significantly to portal hypertension. I expect to confirm through my experiments that the ACE2/Ang 1-7/Mas axis (alternate RAS) is responsible for this vasodilatation and that antagonists targeting this system may have a ro ....The prevalence of liver cirrhosis worldwide is rising due. The majority of the morbidity and mortality, which arises with cirrhosis, occurs due to the development of portal hypertension. In cirrhosis unexplained vasodilatation of the splanchnic circulation occurs contributing significantly to portal hypertension. I expect to confirm through my experiments that the ACE2/Ang 1-7/Mas axis (alternate RAS) is responsible for this vasodilatation and that antagonists targeting this system may have a role in therapy.Read moreRead less
Anti-atherosclerotic Effects Of Angiotensin Fragments & Non-AT1 Receptors: Validation As Innovative Therapeutic Targets
Funder
National Health and Medical Research Council
Funding Amount
$512,065.00
Summary
In Australia the largest cause of death is coronary heart disease (CHD) leading to heart attacks or stroke and claiming a staggering 28,000 lives a year. Atherosclerosis is one of the leading causes of cardiovascular disease, with diseased vessels not able to fully dilate and the plaque that has built up inside these vessels impeding blood flow and possibly rupturing, resulting in heart attacks and stroke. One of the major players in the development and progression of atherosclerosis is the horm ....In Australia the largest cause of death is coronary heart disease (CHD) leading to heart attacks or stroke and claiming a staggering 28,000 lives a year. Atherosclerosis is one of the leading causes of cardiovascular disease, with diseased vessels not able to fully dilate and the plaque that has built up inside these vessels impeding blood flow and possibly rupturing, resulting in heart attacks and stroke. One of the major players in the development and progression of atherosclerosis is the hormone, angiotensin II. Angiotensin II has been found to trigger many factors that cause thickening of the vessel wall, inflammation and imbalances in vasodilator capacity (e.g. oxidative stress and endothelial dysfunction), all of which contribute to atherosclerosis. Clinical trials with drugs that inhibit the formation of angiotensin II (ACE inhibitors), or block the action of angiotensin II (angiotensin receptor antagonists), have demonstrated a significant decrease in mortality in patients with high risk for cardiovascular disease. However their mechanism(s) of action are not fully understood as the circulating levels of shorter fragments of angiotensin II (such as Ang IV and Ang (1-7)) are raised in the blood when these drugs are used and may contribute to the protective effects of these drugs. Importantly, we have found that both Ang IV and Ang (1-7) have protective effects in atherosclerotic blood vessels. Therefore, we hypothesise that fragments of angiotensin II (such as Ang IV and others) exert anti-atherogenic effects via distinct binding sites that oppose the effects caused by angiotensin II, and that these may be partly responsible for the cardio-protective effects of the ACE inhibitors and angiotensin receptor antagonists. Thus, information gained in our study will be useful in directing future prescription practices in clinical management of CHD and stroke, and for designing new therapeutic compounds for the management of atherosclerosis.Read moreRead less
Our studies are aimed at examining how blood flow and pressure is controlled in the various tissues of the body. In particular, we hope to improve our understanding of how blood flow is matched to local metabolic requirements and how a constancy of conditions can be maintained despite changes in overall blood pressure. This ability to control local blood flow occurs through the ability of very small arteries to rapidly adjust their diameters through vasoconstriction or vasodilatation. The vessel ....Our studies are aimed at examining how blood flow and pressure is controlled in the various tissues of the body. In particular, we hope to improve our understanding of how blood flow is matched to local metabolic requirements and how a constancy of conditions can be maintained despite changes in overall blood pressure. This ability to control local blood flow occurs through the ability of very small arteries to rapidly adjust their diameters through vasoconstriction or vasodilatation. The vessels can thus act as valves regulating the transfer of blood flow and pressure to smaller vessels downstream. One particular response that small arteries exhibit is the ability to constrict when pressure within the vessels increases. The increase in pressure appears to stretch the vessel wall which in turn initiates a series of mechanical and biochemical steps that ultimately lead to contraction of muscle cells within the vessel wall. By contracting, the vessels limit the increase in downstream flow and pressure that would be expected to occur. The vessels being studied are very small, typically less than 100 micron. They are studied under isolated and controlled conditions using microscope and computer-based imaging techniques. While this allows us to directly monitor changes in vessel diameter to various stimuli (e.g. a change in pressure) we have also had to miniaturize biochemical measurements so we can understand the chemistry which underlies these vasoconstrictor responses. Understanding of how these local blood regulatory mechanisms occur is not only relevant to our understanding of the normal situation but is also vital to understanding disease states. For example, this work is very relevant to common cardiovascular disorders such as hypertension. It is hoped that a detailed understanding of the biochemical pathways by which small arteries contract will allow the design and targeting of pharmaceutical approaches for treatment of vascular disease states.Read moreRead less
Investigating The Mechanisms That Increase Nerve-evoked Vasoconstriction Following Spinal Cord Injury
Funder
National Health and Medical Research Council
Funding Amount
$372,547.00
Summary
People with spinal cord injury not only lose control of their arms and legs but also lose control of their bladder and bowel. They also have poor control of blood pressure and an overfull bladder or bowel can lead to dangerously high blood pressure. In this project, we are investigating how this abnormal high blood pressure is generated. The aim is to develop treatments which target the mechanisms which increase the blood pressure responses elicited by the bladder and bowel.
Hypertension Induced Inflammation In The Endothelium: The Signalling Pathways Involved
Funder
National Health and Medical Research Council
Funding Amount
$58,313.00
Summary
Patients with high blood pressure are at an increased risk of heart attack and stroke in western societies. It appears that increased pressure induces an inflammation response which leads to the development of atherosclerosis. The aim of this project is to understand the vascular inflammatory mechanisms induced by high blood pressure with the view to prevent blood pressure-related complications such as atherosclerosis.