Project leader: Geoff Head (collaborative project with Andrew Allen)
The regulation of blood pressure is achieved by the complex interaction of neural, hormonal and local control mechanisms. The brain renin-angiotensin system forms part of this very important mechanism for the integration of autonomic response patterns particularly to normal and also to aversive situations. However, the way angiotensin contributes can change and slowly adapt over a time frame of weeks to months. This process is thought to be the key to understanding how the brain can progress to a state of high sympathetic activity associated with hypertension. The difficulty has been to determine the individual contribution of angiotensin peptides in different regions which are often opposing. In collaboration with Andrew Allen at the University of Melbourne, we are using new lentiviral delivery technology combined with the cre-loxP conditional gene deletion to determine the cardiovascular effects of eliminating AT1-receptors in specific nuclei within the brain. We are also determining the cardiovascular effects of expressing normal and constitutively active angiotensin receptors in catecholamine neurons in mice devoid of angiotensin receptors. The transfections last for several months allowing long term using radio telemetry measurement of blood pressure in conscious mice. This project will show us the mechanism by which there is a long term adaptive change in the contribution of angiotensin to autonomic reflex control of blood pressure and where in the brain that process occurs.