Angiotensin AT2 Receptor: A Novel Target For Cardiovascular Modulation
Funder
National Health and Medical Research Council
Funding Amount
$692,040.00
Summary
The hormone, angiotensin II, circulates in the blood and increases blood pressure and thickens the heart and blood vessels, all of which contributes to high blood pressure (hypertension). Angiotensin II causes these excitatory effects by acting at particular target sites called AT1 receptors. Drugs called AT1 receptor antagonists are known to block these excitatory actions of angiotensin II at AT1 receptors. Consequently, these compounds lower blood pressure in humans because they block the ongo ....The hormone, angiotensin II, circulates in the blood and increases blood pressure and thickens the heart and blood vessels, all of which contributes to high blood pressure (hypertension). Angiotensin II causes these excitatory effects by acting at particular target sites called AT1 receptors. Drugs called AT1 receptor antagonists are known to block these excitatory actions of angiotensin II at AT1 receptors. Consequently, these compounds lower blood pressure in humans because they block the ongoing stimulatory action of angiotensin II. However, it is now thought that angiotensin II may also be able to act at another target site (AT2 receptor) to cause opposite effects, i.e. decrease blood pressure and inhibit growth effects. Therefore, this project will examine if direct stimulation of AT2 sites can alter blood flows measured in different body regions in hypertensive rats as part of their mechanism to lower blood pressure. In addition, the effects of continuous stimulation of the AT2 site will be examined in hypertensive rats which will be implanted with a radiotransmitter to measure blood pressure without interference, and afterwards, structural measurements of the heart and blood vessels will be made. Additionally, this project will investigate whether stimulation of the AT2 site also contributes to the blood pressure-lowering effect of drugs already mentioned (AT1 receptor antagonists). The rationale for this is that the hormone angiotensin II is still 'free' to act at the AT2 site, even with AT1 receptors being blocked, and lower blood pressure. These studies will determine if stimulation of AT2 sites contributes to the beneficial effects (i.e. decreased blood pressure and decreased cardiovascular growth) of AT1 receptor antagonists in the treatment of high blood pressure. More importantly, these findings may also identify a new therapeutic target site (AT2 receptor) for drug development in the treatment of cardiovascular disease.Read moreRead less
Therapeutic Relevance Of AT2 Receptors In Cardiovascular Disease And Aging
Funder
National Health and Medical Research Council
Funding Amount
$519,279.00
Summary
Pharmacological modulation of the renin angiotensin system is a cornerstone of evidence-based cardiovascular therapeutics. However, their molecular mechanisms are not entirely clear and some therapeutic options have not been utilized to their full potential. The hormone angiotensin II causes both excitatory and inhibitory cardiovascular effects via distinct binding sites. Of particular importance to contemporary society is the shift in the demographic to a more aged population. In Australia in 2 ....Pharmacological modulation of the renin angiotensin system is a cornerstone of evidence-based cardiovascular therapeutics. However, their molecular mechanisms are not entirely clear and some therapeutic options have not been utilized to their full potential. The hormone angiotensin II causes both excitatory and inhibitory cardiovascular effects via distinct binding sites. Of particular importance to contemporary society is the shift in the demographic to a more aged population. In Australia in 2002, 13% of the population (~2.5 million) were aged 65 years or over, and it has been estimated that this number will increase to 18% (~4 million) by the year 2021. While lipid status and smoking are well known risk factors for cardiovascular disease, advanced age by far confers the greatest risk for cardiovascular disease. In this context, we have found a greater role of the inhibitory angiotensin II binding site in aging that may result from breakdown products of angiotensin II having their own unique effects. This project will determine the relative role of various angiotensin products, and novel compounds that may act similarly, to improve vascular tone and reverse cardiovascular disease in the elderly, hypertensive population.Read moreRead less
Peopling educational policy: realising the new Australian English and mathematics curricula. Implementation of Australian curricula in English and mathematics provides an opportunity for school systems to re-examine practice. This project will identify resources and teacher learning opportunities needed to facilitate implementation of these curricula and use findings to develop interventions identified as likely to optimise implementation.
The Lexicon Project: Analysing pedagogical naming systems from different cultures to reconceptualise classroom practice and advance educational theory. Classrooms remain the principal site of institutionalised learning. Their cultural specificity poses challenges for international comparative research. New approaches are needed. Internationally, our educational theories, research and descriptions of practice are framed in English, which names some aspects of the classroom, but ignores key aspect ....The Lexicon Project: Analysing pedagogical naming systems from different cultures to reconceptualise classroom practice and advance educational theory. Classrooms remain the principal site of institutionalised learning. Their cultural specificity poses challenges for international comparative research. New approaches are needed. Internationally, our educational theories, research and descriptions of practice are framed in English, which names some aspects of the classroom, but ignores key aspects named in other languages. This limits our capacity to access, connect and adapt the wisdom of other cultures. The Lexicon Project will initiate cross-cultural dialogue to identify pedagogical terms from selected Asian and European educational communities and use these as analytical tools to categorise, interrogate and enrich our classroom practice, classroom research, and educational theorising.Read moreRead less