Pathophysiological Significance of Angiotensin II Receptor Subtype in Human Adrenals

The adrenal gland is one of the major target organs of angiotensin II (Ang II). However, the pathophysiological significance of the Ang II receptor subtypes, AT1 and AT2, in human adrenals has not been elucidated. We investigated the mRNA expression of each receptor subtype and their role in steroid secretion in human adrenals. Expression levels of AT1 and AT2 receptor mRNA were determined by reverse transcription-polymerase chain reaction followed by Southern blot analysis of normal adrenocortical tissues (n=6) and several adrenal tumor tissues : aldosterone-producing adrenocortical adenoma (n=6), Cushing's syndrome (n=6), and pheochromocytoma (n=6). Steroid secretion was examined in vitro by incubating tissue with Ang II (1μM) or the selective AT2 agonist CGP-42112 (1μM) in the presence or absence of the selective AT1 antagonist CV-11974 (1μM). mRNA expression of both receptor subtypes was demonstrated in all human adrenal tissues examined. The expression levels of AT1 and AT2 mRNA tended to be higher in tumor tissues compared to normal tissues. Ang II-induced aldosterone secretion was suppressed 50% by the addition of CV-11974. CGP-42112 increased aldosterone secretion by 55% over the control, which was not suppressed by CV-11974. Incubation of adrenal tissues with Ang II or CGP-42112 did not affect cortisol secretion. These results suggest that AT2, as well as AT1, may be involved in the stimulation of aldosterone secretion and tumorigenesis of the human adrenals