REGULATION OF ANGIOTENSINOGEN GENE-EXPRESSION IN THE RAT FOREBRAIN BYADRENAL-STEROIDS AND RELATION TO SALT APPETITE

The renin-angiotensin system (RAS) is present in the brain where it pa rticipates in regulation of fluid-electrolyte homeostasis and possibly plays a role in arousal of salt appetite. In the present studies usin g quantitative in situ hybridization histochemistry we examined the le vel of the angiotensinogen (ANG) mRNA in the forebrain areas associate d with fluid-electrolyte balance in adrenalectomized (ADX) rats and AD X rats supplemented either with selective glucocorticoid type II recep tor agonist RU 28362 or with the selective type I receptor agonist, al dosterone (ALDO). RU 28362 and ALDO were administered for 7 days via A lzet 2001 osmotic minipumps at the rates of 10 mu g/mu l/h and 1 mu g/ mu l/h, respectively, Following adrenalectomy, rats were maintained on a standard rat chow, water and 3% NaCl ad lib. In situ hybridization was performed either with a synthetic [P-33]- Or [P-32]-3' end-labeled oligonucleotide probe and the level of ANG mRNA was detected by grain counting over a single cell or by quantitative film autoradiography, respectively. Seven days post ADX the ANG mRNA level in all studied fo rebrain areas-septum-diagonal band of Broca (SEPT/DBB), the areas imme diately adjacent to the organum vasculosum of the lamina terminalis (O VLT), the median preoptic nucleus (MnPO), and the medial preoptic area (mPOA) -of ADX rats decreased by 50-60%. ALDO treatment, which did pr event ADX-induced saline ingestion, did not prevent this decrease. How ever, supplementation with RU 28362 maintained normal levels of ANG mR NA in all the above regions of the brain. Thus the expression of the A NG gene in the studied areas of rat forebrain is predominantly under t he control of the adrenal glucocorticoids via the type II receptor and not regulated by an ALDO dose that stabilizes natriuresis from the ki dney.