Much evidence exists for the presence of an endogenous brain renin-angiotensin system, yet knowledge of its regulation is rudimentary. It is important to understand the factors which can functionally alter the brain renin-angiotensin system since it is known to influence blood pressure, thirst, salt appetite, secretion of antidiuretic hormone and secretion of ACTH. The overall aim of this proposal is to assess the role of steroids in the regulation of the brain renin-angiotensin system since background evidence and preliminary studies from our laboratories suggest that mineralocorticoids, glucocorticoids and estrogenic agents may play a role. Studies will be carried out both in vivo and in vitro using brain cell cultures.
The specific aims are: (1) to compare the effects of mineralocorticoids and glucocorticoids on the regulation of all aspects of the brain renin-angiotensin system in vivo and in vitro; i.e., angiotensin II (Ang II) levels, Ang II turnover, Ang II receptors, renin, and angiotensin converting enzyme levels; (2) to determine whether these steroids functionally alter the brain renin-angiotensin system. The effects of different steroids on central Ang II-receptor-mediated events will be examined, i.e. the pressor and drinking responses to centrally injected Ang II in vivo and the effects of steroids on Ang II-stimulated neuronal (3H)-norepinephrine transport and monoamine oxidase activity in vitro; and (3) to determine the cellular mechanisms by which these steroids regulate central Ang II receptors in vitro. Both in vivo and in vitro studies will be used to determine whether there is a potential role for catecholamines in mediating the effects of steroids on central Ang II receptors. This project will provide fundamental information regarding mineralocorticoid and glucocorticoid interactions with the brain renin-angiotensin system. In view of the powerful action of Ang II in the brain and its implied involvement in regulation of blood pressure, fluid and electrolyte homeostasis, and hormonal secretion, knowledge of the way in which the brain renin- angiotensin system is regulated by steroids will be a strong contribution to our understanding of the factors involved in these physiological events.
