Regulation of angiotensin II type 2 receptor gene expression in the adrenal medulla by acute and repeated immobilization stress

Abstract

While the renin–angiotensin system is important for adrenomedullary responses to stress, the involvement of specific angiotensin II (Ang II) receptor subtypes is unclear. We examined gene expression changes of angiotensin II type 1A (AT1A) and type 2 (AT2) receptors in rat adrenal medulla in response to immobilization stress (IMO). AT2receptor mRNA levels decreased immediately after a single 2-h IMO. Repeated IMO also decreased AT2receptor mRNA levels, but the decline was more transient. AT1Areceptor mRNA levels were unaltered with either single or repeated IMO, although binding was increased following repeated IMO. These effects of stress on Ang II receptor expression may alter catecholamine biosynthesis, as tyrosine hydroxylase and dopamine β-hydroxylase mRNA levels in PC12 cells are decreased with Ang II treatment in the presence of ZD7155 (AT1receptor antagonist) or with CGP42112 (AT2receptor agonist) treatment. Involvement of stress-triggered activation of the hypothalamic–pituitary–adrenocortical or sympathoadrenal axis in AT2receptor downregulation was examined. Cultured cells treated with the synthetic glucocorticoid dexamethasone displayed a transcriptionally mediated decrease in AT2receptor mRNA levels. However, glucocorticoids are not required for the immediate stress-triggered decrease in AT2receptor gene expression, as demonstrated in corticotropin-releasing hormone knockout (CrhKO) mice and hypophysectomized rats, although they can regulate basal gene expression. cAMP and pituitary adenylate cyclase-activating polypeptide also reduced AT2receptor gene expression and may mediate this response. Overall, the effects of stress on adrenomedullary AT1Aand AT2receptor expression may contribute to allostatic changes, such as regulation of catecholamine biosynthesis.