ANGIOTENSIN-II RECEPTOR SUBTYPES ON ADRENAL ADENOMA IN PRIMARY HYPERALDOSTERONISM

Patients with an aldosterone-producing adenoma (APA) characteristicall y fail to show an increase in plasma aldosterone (PA) concentration wi th maneuvers that increase angiotensin II (Ang II), yet they retain a brisk response of PA to adrenocorticotrophic hormone. Therefore, adren al Ang II receptor binding was characterized in a patient with APA who had a blocked PA response to Ang II infusion before adrenalectomy. Th e binding of (I-125)Sar1,Ile5-Ang II in adrenal gland and tumor was fu lly displaced by excess Ang II. In the tumor, 98% of (I-125)Sar1,Ile5- Ang II binding was displaced by the AT1 receptor antagonist losartan, yet only 5% was displaced by the AT2 receptor antagonist PD-123,319. A utoradiography of the adrenal gland itself showed a predominance of AT 1 receptors in the cortex and AT2 receptors in the medulla. The tumor showed a predominance of AT1 receptors, but there was some evidence of a limited population of AT2 receptors. The tumor and adjacent adrenal contained high concentrations of Ang II. In conclusion, a defect in A ng II-stimulated aldosterone secretion in APA occurs despite high conc entrations of Ang II in the adrenal and the presence of specific, high -affinity Ang II receptor binding sites.