Angiotensin II receptor subtypes on adrenal adenoma in primary hyperaldosteronism.
Patients with an aldosterone-producing adenoma (APA) characteristically fail to show an increase in plasma aldosterone (PA) concentration with maneuvers that increase angiotensin II (Ang II), yet they retain a brisk response of PA to adrenocorticotrophic hormone. Therefore, adrenal Ang II receptor binding was characterized in a patient with APA who had a blocked PA response to Ang II infusion before adrenalectomy. The binding of [125I]Sar1,IIe5-Ang II in adrenal gland and tumor was fully displaced by excess Ang II. In the tumor, 98% of [125I]Sar1,IIe5-Ang II binding was displaced by the AT, receptor antagonist losartan, yet only 5% was displaced by the AT2 receptor antagonist PD-123,319. Autoradiography of the adrenal gland itself showed a predominance of AT1 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 Ang II-stimulated aldosterone secretion in APA occurs despite high concentrations of Ang II in the adrenal and the presence of specific, high-affinity Ang II receptor binding sites.
Cook
M D
MD
Division of Nephrology, Hypertension, and Transplantation, University of Florida, Gainesville 32610.
Phillips
M I
MI
Cook
V I
VI
Kimura
B
B
Wilcox
C S
CS
D000236:Adenoma / Q000378:metabolism*; D000310:Adrenal Gland Neoplasms / Q000378:metabolism*; D000324:Adrenocorticotropic Hormone / Q000494:pharmacology; D000450:Aldosterone / Q000097:blood; D000804:Angiotensin II / Q000097:blood / Q000494:pharmacology; D057911:Angiotensin Receptor Antagonists; D001345:Autoradiography; D001667:Binding, Competitive; D001713:Biphenyl Compounds / Q000494:pharmacology; D006801:Humans; D006929:Hyperaldosteronism / Q000378:metabolism*; D007093:Imidazoles / Q000494:pharmacology; D019808:Losartan; D008297:Male; D008875:Middle Aged; D011725:Pyridines / Q000494:pharmacology; D011945:Receptors, Angiotensin / Q000145:classification / Q000378:metabolism*; D013777:Tetrazoles / Q000494:pharmacology
D057911:Angiotensin Receptor Antagonists; D001713:Biphenyl Compounds; D007093:Imidazoles; D011725:Pyridines; D011945:Receptors, Angiotensin; D013777:Tetrazoles; D000804:Angiotensin II; C073402:PD 123319; D000450:Aldosterone; D000324:Adrenocorticotropic Hormone; D019808:Losartan