Oral Presentation Neuropathophysiology - an ISH satellite 2012

Contribution of central angiotensin to the cardiovascular response to aversive stress. (#25)

Geoffrey A Head 1
  1. Baker IDI Heart and Diabetes Institute, Melbourne, VIC, Australia
Brain angiotensin has been recognized as an important neuromodulator of the cardiovascular response induced by aversive stress. Angiotensin receptors of mainly the AT1 receptor type are located in district forebrain, brainstem and spinal cord regions known to regulate cardiovascular reflexes, sympathetic vasomotor activity and blood pressure. The rostral (RVLM) and caudal ventrolateral medulla (CVLM) and the nucleus tractus solitarius (NTS) are important regions for autonomic regulation and are rich in AT1 receptors. We have shown that blockade of AT1 receptor in the dorsomedial hypothalamus and the RVLM of conscious rabbits attenuates the pressor response to stress. We have also shown that mice lacking AT1 receptors have reduced pressor responses to stress that is associated with less activation on neurons in the hypothalamus but greater activation of cells in the CVLM and NTS. Our recent studies have involved transfection of AT1 receptors into the RVLM, CVLM and the NTS of mice lacking AT1 receptors. Bilateral microinjections of lentivirus with the catecholamine-selective PRSx8 promoter driving expression of either green fluorescent protein (GFPv asĀ  control) or AT1 receptors into the RVLM increased the pressor response to restraint stress. By contrast, the same injections of AT1 receptors into the CVLM, reduced the pressor response to stress and increased baroreflex sensitivity. Expression of AT1 receptors into the NTS increased blood pressure for several weeks but surprisingly had little effect on the pressor response to stress or on the baroreflex. These results suggest that the angiotensin within the forebrain and brainstem plays an important role in modulating the cardiovascular response to stress and also contributes to long term levels of blood pressure levels.