ANGIOTENSIN-II AND THE ADRENAL

1. Angiotensin II (AngII) evokes a variety of physiological responses in the adrenal gland, It is the major regulator of aldosterone secreti on, in the medulla it enhances catecholamine release and it exerts tro phic effects in the adrenal and stimulates growth factor secretion, 2. Angiotensin II acts via binding to specific receptors, located on the plasma membrane, Two pharmacologically distinct AngII receptor subtyp es, type 1 (AT(1)) and type 2 (AT(2)) receptors, have been identified using the non-peptide antagonists Dup753 and PD 123177, respectively, and cDNA encoding each type have been identified, 3, In the adrenal, t he AT(1) receptor modulates all the known biological effects of AngII. The expression of the AT(1) receptor is modulated at the mRNA and pro tein levels by many factors: conditions that increase levels of AngII (low sodium diet, renovascular hypertension, AngII infusion) up-regula te AT(1) receptor mRNA levels and binding and increase aldosterone sec retion. 4, A tissue renin-angiotensin system has been found in the adr enal, suggesting an important paracrine role for AngII in aldosterone regulation, 5. The possible involvement of AT(1) receptors in human di sease has been investigated by examining the role of AngII receptors i n adrenal tumours. Binding and gene expression studies have shown that AngII receptors are abundantly expressed in aldosterone-producing ade noma (APA), 6. Densitometric analysis of AT(1) expression in APA showe d no significant differences compared with normal and nontumorous adre nal. In addition, no mutations in the coding sequence of the AT(1) rec eptor have been found to date in adrenal tumours.