Antiadrenergic autoimmunity in postural tachycardia syndrome.

ABSTRACT: Aims:Postural tachycardia syndrome (POTS), a common and debilitating cardiovascular disorder, is characterized by an exaggerated heart rate increase during orthostasis and a wide spectrum of adrenergic-related symptoms. To determine the aetiology of POTS, we examined a possible pathophysiological role for autoantibodies against ?1-adrenergic (?1AR) and ?1/2-adrenergic receptors (?1/2AR). Methods and results:Immunoglobulin G (IgG) derived from 17 POTS patients, 7 with recurrent vasovagal syncope (VVS), and 11 normal controls was analysed for its ability to modulate activity and ligand responsiveness of ?1AR and ?1/2AR in transfected cells and to alter contractility of isolated rat cremaster arterioles in vitro. Immunoglobulin G activation of ?1AR and ?1/2AR was significantly higher in POTS compared with VVS and controls in cell-based assays. Eight, 11, and 12 of the 17 POTS patients possessed autoantibodies that activated ?1AR, ?1AR and ?2AR, respectively. Pharmacological blockade suppressed IgG-induced activation of ?1AR and ?1/2AR. Eight of 17 POTS IgG decreased the ?1AR responsiveness to phenylephrine and 13 of 17 POTS IgG increased the ?1AR responsiveness to isoproterenol irrespective of their ability to directly activate their receptors. Postural tachycardia syndrome IgG contracted rat cremaster arterioles, which was reversed by ?1AR blockade. The upright heart rate correlated with IgG-mediated ?1AR and ?1AR activity but not with ?2AR activity. Conclusion:These data confirm a strong relationship between adrenergic autoantibodies and POTS. They support the concept that allosteric-mediated shifts in the ?1AR and ?1AR responsiveness are important in the pathophysiology of postural tachycardia.

SUBMITTER: Fedorowski A 

PROVIDER: S-EPMC5834103 | biostudies-literature | 2017 Jul

REPOSITORIES: biostudies-literature