Postgraduate Studies Projects

Lab Head: Assoc Prof Markus Schlaich

Phone: 8532 1502

Email: markus.schlaich@bakeridi.edu.au

The main focus the Neurovascular Hypertension & Kidney Disease Laboratory is to investigate the mechanisms that link chronic and end stage renal disease with the very high rate of cardiovascular conditions such as hypertension, left ventricular hypertrophy, heart attacks, heart failure, and sudden cardiac death in this group of patients. In close collaboration with the Human Neurotransmitters Lab we are particularly interested in investigating the role of the sympathetic nervous system (SNS) in this setting and exploring novel therapeutic strategies to reduce the large burden of cardiovascular disease in patients with renal failure.

We have a variety of ongoing and planned projects that are suitable for both Honours and PhD candidates, particularly with a medical background. The majority of our studies are clinically orientated and many involve direct patient/volunteer contact. We apply a large variety of clinical methods to study sympathetic activity (catheter based assessment of noradrenaline kinetics, microneurography, baroreflex sensitivity), vascular and endothelial function (both invasively and non-invasively using ultrasound, forearm occlusion plethysmography, EndoPat...), cardiac structure and function (echocardiography, MRI...), and others. In combining these clinical studies with genetic, protein based and biochemical testing from plasma samples and biopsy specimens we cover the relevant spectrum to perform translational research. I would be more than happy to discuss the research topics and specific projects in the areas described below in more detail with interested students.

Sympathetic activation in renal disease

Chronic kidney disease is a huge health problem affecting around 2 million Australians. The factors that are responsible for initiation and progression of renal failure are only incompletely understood. Experimental evidence suggests that increased activity of sympathetic nerves contributes to the deterioration of renal function and that afferent signals from the diseased or injured kidney(s) to the brain are crucial in maintaining a high sympathetic tone that is directed not only to the kidneys but also to other vital organs such as the heart and to the vasculature. Adverse consequences of sympathetic activation include progression of kidney disease, increase of blood pressure, enlargement of the heart, heart failure and cardiac arrhythmias. All these clinical features are very common in patients with renal failure. Using state of the art techniques to assess sympathetic activation in patients with various degrees of renal failure our lab aims to establish that this link is evident in humans which would form the basis for novel treatment strategies of renal failure and its consequences by inhibiting the sympathetic nervous system.

Sympathetic denervation

Surgical procedures to disrupt sympathetic nerves have been applied very successfully since the early 1950s to treat patients with very high levels of blood pressure. With the availability of potent pharmaceutical drugs to lower blood pressure, these procedures were abandoned due to their invasiveness and the risks and side effects associated with the procedure. Nevertheless, the concept of specific sympathetic denervation is intriguing and has recently gained considerable interest with the availability of a novel catheter based technology to directly disrupt renal sympathetic nerves. We are currently involved in two clinical trials that assess the safety and efficacy of such an approach to lower blood pressure in patients with resistant hypertension (uncontrolled blood pressure despite extensive drug treatment) and in patients with end stage renal disease.         

Endothelial function in chronic and end stage renal disease

The endothelium is the inner layer of our blood vessels and plays a crucial role in the regulation of vascular tone mainly via synthesis and release of nitric oxide (NO), which is a very potent vasodilator. L-arginine is the substrate for NO synthase to form NO and there is evidence from patients with heart failure and hypertension that the transport of L-arginine across the cell membrane is altered and contributes to endothelial dysfunction in these conditions. Wether this is also the case in patients with renal disease has not yet been investigated. Using established methods to assess L-arginine transport in vivo (³H-L-arginine kinetics) and in vitro (mononuclear cells) as well as endothelial function by forearm plethysmography we aim to test the hypothesis that substrate deficiency contributes substantially to altered endothelial function in patients with renal disease. 

Resistant hypertension

Uncontrolled high blood pressure despite extensive drug treatment is a severe problem in the large cohort of patients suffering from high blood pressure (hypertension), which affects around 35-40% of the Australian population. Uncontrolled high blood pressure dramatically increases the risk for cardiovascular morbidity and mortality. The reasons why some patients do not respond to potent drugs that achieve control of blood pressure in many other hypertensive patients are largely unknown. In an attempt to better characterize these patients we aim to comprehensively assess their clinical phenotype and combine these data with results from our profiling facilities to unravel the mechanisms responsible for their resistance to common antihypertensive drugs, which may also help to identify novel treatment targets in this patient cohort.