Therapeutic relevance of AT2 receptors in cardiovascular disease and aging

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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.