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RENAL VASCULAR HYPERTROPHY AND REMODELLING IN SHR: SYMPATHETIC NERVOUS SYSTEM AND IMPLICATIONS FOR HYPERTENSION
Funder
National Health and Medical Research Council
Funding Amount
$191,561.00
Summary
High blood pressure (hypertension) remains a major health problem for Australians. One in six Australians suffer from hypertension, with consequent increased risk of stroke and heart attack. Anti-hypertensive treatments are available, but must usually be taken for the rest of the patient's life and the cost to the taxpayer of anti-hypertensive drugs is greater than for any other health problem. Prevention of high blood pressure depends on identifying the initial cause - but we still do not know ....High blood pressure (hypertension) remains a major health problem for Australians. One in six Australians suffer from hypertension, with consequent increased risk of stroke and heart attack. Anti-hypertensive treatments are available, but must usually be taken for the rest of the patient's life and the cost to the taxpayer of anti-hypertensive drugs is greater than for any other health problem. Prevention of high blood pressure depends on identifying the initial cause - but we still do not know the cause in over 90% of hypertensive people. This project will study whether overactivity of the nerves to the blood vessels of the kidney might be the cause. There is evidence for this in humans, and in a strain of rats which develops high blood pressure (the spontaneously hypertensive rat). Our experiments will study these rats to see whether nerves affect the structure and function of the blood vessels of the kidney in ways that lead to increased blood pressure.Read moreRead less
ACE2, A New Regulator Of The Renin Angiotensin System
Funder
National Health and Medical Research Council
Funding Amount
$492,625.00
Summary
Angiotensin converting enzyme (ACE) is a key enzyme in the renin-angiotensin system (RAS), converting Angiotensin I to the potent vasoconstrictor Angiotensin II (Ang II). ACE inhibitors have been highly successful in the management of hypertension, are standard therapy following myocardial infarction to delay the development of heart failure, and also reduce the rate of progression of renal disease. Recently, a novel enzyme called ACE2 has been discovered in the heart and kidneys. Unlike ACE, AC ....Angiotensin converting enzyme (ACE) is a key enzyme in the renin-angiotensin system (RAS), converting Angiotensin I to the potent vasoconstrictor Angiotensin II (Ang II). ACE inhibitors have been highly successful in the management of hypertension, are standard therapy following myocardial infarction to delay the development of heart failure, and also reduce the rate of progression of renal disease. Recently, a novel enzyme called ACE2 has been discovered in the heart and kidneys. Unlike ACE, ACE2 causes the formation of the vasodilator, Ang 1-7. We have data in the heart and the kidney that supports the concept that ACE2 acts in a counter-regulatory manner to ACE. We suggest that ACE2 may play an important role to modulate the balance between vasoconstrictors and vasodilators in the heart and kidney. The studies detailed in this proposal are designed to specifically examine the role and regulation of ACE2 in the healthy heart and kidney as well as in cardiovascular and renal disease. The project brings together two groups with complementary skills and techniques, both of whom have collaborations with the discoverers of ACE2, and who have been exploring the role of ACE2 as evidenced from our recent publication (Tikellis et al, Hypertension in press, 2003).Read moreRead less
Effects Of Risk Factor Control On Atherosclerosis, Vasoreactivity And Cardiac Ischemia In Patients On Dialysis
Funder
National Health and Medical Research Council
Funding Amount
$212,126.00
Summary
End-stage renal failure is one of the commonest serious chronic diseases; in Australia, over 10,000 patients are in dialysis programs or have functioning transplants. The commonest cause of death in this patient group is coronary artery disease, and attempts are routinely made to identify patients with this problem, with the intent of controlling this risk by angioplasty or bypass surgery. Unfortunately, these procedures may be less effective than usual, because the process of artery narrowing i ....End-stage renal failure is one of the commonest serious chronic diseases; in Australia, over 10,000 patients are in dialysis programs or have functioning transplants. The commonest cause of death in this patient group is coronary artery disease, and attempts are routinely made to identify patients with this problem, with the intent of controlling this risk by angioplasty or bypass surgery. Unfortunately, these procedures may be less effective than usual, because the process of artery narrowing is more aggressive in patients with renal disease. Moreover, this process may cause patients with negative testing for coronary disease at one point in time to develop coronary problems over follow-up. In this study, we propose to use a standard stress testing protocol to stratify the risk of coronary events in a group of at risk patients on dialysis. Those at highest risk will undergo bypass surgery, while those at intermediate and low risk will be randomized to usual care, or an aggressive treatment of atheroma with cholesterol reduction, folic acid supplementation (aiming to normalize homocysteine), blood pressure and blood sugar control. The effects of this approach will be followed by examination of biochemical markers of atherosclerosis, and imaging of arterial thickness and reactivity (reflecting tests of structure and function of the vasculature). We will also assess of the progression or reduction of abnormal cardiac stress responses, and the occurence of events at follow-up. Finally, follow-up data will be used to compare the predictive value of the 2 stress testing protocols. The results of this study will enhance our understanding of the importance of the atherosclerotic process in renal patients, and move the management approach for coronary disease in renal failure toward active risk factor control and away from revascularization.Read moreRead less
Effects Of Omega-3 Fatty Acids And Coenzyme Q10 On Cardiovascular Risk In Chronic Renal Failure
Funder
National Health and Medical Research Council
Funding Amount
$433,725.00
Summary
Heart disease is one of the main causes of death in Australia. People with chronic renal failure (CRF) are at increased cardiovascular risk due to the coexistence of hypertension (high blood pressure), blood lipid abnormalities, and increased inflammation and oxidative stress. One approach may be to complement drug treatment of CRF with non-drug measures such as nutrition and lifestyle factors. In this regard, omega-3 fatty acids have great clinical potential in the treatment of CRF and its asso ....Heart disease is one of the main causes of death in Australia. People with chronic renal failure (CRF) are at increased cardiovascular risk due to the coexistence of hypertension (high blood pressure), blood lipid abnormalities, and increased inflammation and oxidative stress. One approach may be to complement drug treatment of CRF with non-drug measures such as nutrition and lifestyle factors. In this regard, omega-3 fatty acids have great clinical potential in the treatment of CRF and its associated complications. Omega-3 fatty acids reduce blood pressure and blood vessel wall elasticity, they improve blood fats, reduce the tendency of blood to clot, and attenuate inflammation and oxidative stress. Coenzyme Q10 is an antioxidant that plays a critical role in cellular function. It improves blood pressure, blood vessel and heart function, and glucose control. It is proposed that the impact of a combined approach of supplementation of omega-3 fatty acids given as fish oils and coenzyme Q10, will lead to beneficial composite effects on blood pressure and heart disease risk in patients with mild-to-moderate chronic renal failure. In the proposed study, patients will undergo medical and biochemical assessment during a 3-week baseline period, after which they will be allocated to either supplement their normal diet with either 4g of encapsulated fish oil or placebo per day. Within each of these groups they will be further assigned to take coenzyme Q10 capsules (200mg) or placebo capsules. All measurements will be repeated at the end of 8 weeks.Read moreRead less
Evaluation Of Cardiac Risk And Alterations In Cardiovascular Structure And Function In Renal Transplantation
Funder
National Health and Medical Research Council
Funding Amount
$72,275.00
Summary
Despite recent advances in health care, cardiovascular disease remains the leading killer of patients with Renal Failure and following Renal Transplantation. Current methods for assessing Cardiovascular Risk largely rely on tests that utilise radiation and-or kidney-toxic substances. Recent advances in Magnetic Resonance Imaging may allow for more accurate and safer assessment of Cardiovascular Risk and improve our understanding of the effect of Renal Transplantation on the Cardiovascular System