Angiotensin AT2 receptor: a novel target for cardiovascular modulation [ 2001 - 2005 ]

Research Grant

Researchers: Prof Robert Widdop (Principal investigator)

Brief description 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.

Funding Amount $AUD 692,040.16

Funding Scheme NHMRC Project Grants

Notes Standard Project with Research Fellowship