Proceedings of the Symposium ‘Angiotensin AT1 Receptors: From Molecular Physiology to Therapeutics’: ANGIOTENSIN II AND THE ADRENAL

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Abstract
1. Angiotensin II (AngII) evokes a variety of physiological responses in the adrenal gland. It is the major regulator of aldosterone secretion, in the medulla it enhances catecholamine release and it exerts trophic 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 subtypes, 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, the AT(1) receptor modulates all the known biological effects of AngII. The expression of the AT(1) receptor is modulated at the mRNA and protein levels by many factors: conditions that increase levels of AngII (low sodium diet, renovascular hypertension, AngII infusion) up-regulate AT(1) receptor mRNA levels and binding and increase aldosterone secretion. 4. A tissue renin-angiotensin system has been found in the adrenal, suggesting an important paracrine role for AngII in aldosterone regulation. 5. The possible involvement of AT(1) receptors in human disease has been investigated by examining the role of AngII receptors in adrenal tumours. Binding and gene expression studies have shown that AngII receptors are abundantly expressed in aldosterone-producing adenoma (APA). 6. Densitometric analysis of AT(1) expression in APA showed no significant differences compared with normal and nontumorous adrenal. In addition, no mutations in the coding sequence of the AT(1) receptor have been found to date in adrenal tumours.