Abstract 16585: Activating Autoantibodies to the AT1R Are Present in “Primary” Hyperaldosteronism
Introduction: Activating autoantibodies to the second extracellular loop of the angiotensin II type 1 receptor (AT1R) are present in some hypertensive subjects.
Hypothesis: Anti-AT1R autoantibodies are elevated in subjects with primary hyperaldosteronism (PHA) including idiopathic adrenal hyperplasia (IAH) and aldosterone-producing adenomas (APA).
Methods: A MAP-AT1R peptide (AFHYESQ) ELISA was used to screen 5 normal subjects and 14 with biochemically confirmed PHA (3 surgically documented APA, 4 probable IAH based on non-lateralization by adrenal venous sampling and 7 who were not operative candidates and did not undergo adrenal sampling (indeterminate, IPHA). AT1R autoantibody activity in IgG was analyzed using a cell-based assay for activation of transfected AT1R (DiscoveRx) and expressed as % of baseline.
Results: Specific autoantibodies against AT1R MAP-peptide were increased in 2/4 IAH and 4/7 with IPHA; but 0/3 with APA when compared to normal controls. IgG from patient sera (but not normal control sera) and Ang II separately increased AT1R activity in AT1R transfected cells in a dosage dependent fashion. Activity was blocked by 10 µM losartan. AT1R activation by IgG was significantly increased in IAH (127.6±6.0%, n=4), APA (132.1±4.8, n=3) and IPHA (128.9±5.7%, n=7) compared to normal controls (118.7±7.4%, n=5). Active anti-AT1R IgG functionally constricted perfused rat cremaster arterioles in vitro which was blocked by 10 µM losartan.
Conclusions: Autoantibodies directed to AT1R are elevated in some patients with PHA. IgG antibodies from each PHA group activated the AT1R and possessed pressor activity in resistance arteries in vitro. Anti-ATR1 peptide antibody detected by ELISA was only partially predictive of activity due to antibody avidity or specificity. Autoantibody activation of AT1R when present has a probable pressor role in both IAH and APA; and their presence in both entities would lead to increased aldosterone production and/or concurrent hyperplasia.
- © 2012 by American Heart Association, Inc.