Mineralocorticoids modulate central angiotensin II receptors in rats

Abstract

The effect of chronic administration of deoxycorticosterone acetate (DOCA) on the regulation of angiotensin II (AII) receptors in the brains of adult rats was compared with their drinking and pressor responsiveness to both peripheral and central administration of AII. Analysis of AII receptor binding in a block of tissue containing the hypothalamus, thalamus and septum (HTS) after treatment for 8 weeks with DOCA-salt (240 μg/kg/day) revealed a significant increase in the number of AII-binding sites compared to salt-loaded controls (B max 9.65 vs 6.80 fmol/mg protein) and no change in binding affinity (K d) . Significant increases in the drinking responses to peripheral (200 μg/kg) and central (10 ng) administration of AII were observed in these rats. Additional studies indicated that the pressor responses to either centrally (25 ng) or peripherally (20 μg/kg, s.c.) administered AII were augmented in DOCA-treated rats. The effect of mineralocorticoids on AII-binding sites was also investigated in primary neuronal cultures from the brains of one-day-old rats. Pretreatment of these cultures with either DOCA or aldosterone (ALDO) induced a time- and concentration-dependent increase in the specific binding of [ 125I]AII. Maximal increases in AII binding of 53 and 62% above control values were observed when cultures were treated with 500 pg of either ALDO or DOCA per milliliter of culture medium. Scatchard analysis of specific binding of [ 125I]AII in neuronal cultures treated with DOCA revealed a significant increase in B max but no change in K d . Thus, mineralocorticoid hormones induce an increase in the number of AII-receptor binding sites in the HTS of rats which parallels physiological responses to both central and peripheral administration of AII. This relationship may be independent of the concentration of AII in the blood, since an increase in the number of AII binding sites was also observed in neurons cultured from the brains of one-day-old rats which had been treated with mineralocrticoid hormones.