It has been demonstrated that the brain contains a renin/angiotensin system which influences the central control of blood pressure. Considerable evidence suggests that catecholamines interact with angiotensin in the central regulation of blood pressure. We have formulated the hypothesis that catecholamines and angiotensin interact in a negative feedback manner.
We aim to examine this angiotensin II/catecholamine interaction in a novel way, using cultured brain neurons. This system allows us to investigate the nature of angiotensin II/catecholamine interactions at the cellular level in intact neurons, without the complications of animal behavior or stress. Cells will be cultured from brainstem and hypothalamus of one day old rats, areas which contain both catecholaminergic and angiotesin II immunoreactive neurons, and which are involved in cardiovascular control. Cells will be grown for 21 days, and then used for experiments. The effects of angiotensin II on catecholamine neurotransmission will be examined, eg. on catecholamine release, synthesis, uptake and metabolism, and on Alpha and Beta adrenergic receptor binding. Also, the effects of this peptide on catecholamine dependant adenylate cyclase will be determined. Conversely, angiotensin II synthesis, receptor binding and stimulation of lipid metabolism will be examined in the presence of altered catecholamine transmission, eg. catecholamine agonists, antagonists and other agents that enhance or block catecholaminergic activity. The results obtained will determine whether angiotensin II and catecholamines interact in a negative feedback manner, or otherwise, and in the final stages will be related to in vivo studies. In the long term this study will provide fundamental information regarding angiotensin II/catecholamine interactions at the cellular level, and the role of these interactions in blood pressure regulation. The results also have implications for understanding the central mechanisms involved in hypertension.
Showing the most recent 10 out of 70 publications
