title: Autoantibody activation of beta-adrenergic and muscarinic receptors contributes to an "autoimmune" orthostatic hypotension.
abstract: BACKGROUND
  Orthostatic hypotension (OH) is characterized by an abnormal autonomic response to upright posture. Activating autoantibodies to β1/2-adrenergic (AAβ1/2AR) and M2/3 muscarinic receptors (AAM2/3R) produce vasodilative changes in the vasculature that may contribute to OH.
  
  
  METHODS
  Immunoglobulin (Ig)G from 6 patients with idiopathic OH harboring autoantibodies and from 10 healthy control subjects were examined for: 1) β1AR and M2R activity with a perfused Purkinje fiber assay and PKA assay in H9c2 cells and 2) vasodilator β2AR and M3R activity using a pressurized cremaster resistance arteriole assay. Changes in IgG activity with and without propranolol, atropine, and L-NAME were used to estimate AAβAR, AAM2R, and AAM3R activation of their respective functions.
  
  
  RESULTS
  All six patients had elevated enzyme-linked immunosorbent assay titers to at least one of the receptors compared with controls. βAR-mediated contractility activity and M2R activity were increased in five of the six patients. IgG from all six patients produced a direct vasodilator effect on cremaster arterioles. βAR and nitric oxide synthase blockade led to near normalization of IgG-induced vasodilation.
  
  
  CONCLUSIONS
  AAβ1/2AR and AAM2/3R are present in some patients with idiopathic OH compatible with an in vivo effect. These autoantibodies and their cardiovascular effects provide new mechanistic insights into the pathophysiology of OH.
authors: Heart Rhythm Institute, University of Oklahoma Health Sciences Center and VA Medical Center, Oklahoma City, OK, USA.
authors: Xichun
authors: X
authors: Yu
authors: Stavros
authors: S
authors: Stavrakis
authors: Michael A
authors: MA
authors: Hill
authors: Shijun
authors: S
authors: Huang
authors: Sean
authors: S
authors: Reim
authors: Hongliang
authors: H
authors: Li
authors: Muneer
authors: M
authors: Khan
authors: Sean
authors: S
authors: Hamlett
authors: Madeleine W
authors: MW
authors: Cunningham
authors: David C
authors: DC
authors: Kem
mesh_terms: D000368:Aged; D001323:Autoantibodies / Q000097:blood*; D016022:Case-Control Studies; D005260:Female; D006801:Humans; D007024:Hypotension, Orthostatic / Q000097:blood / Q000276:immunology* / Q000503:physiopathology*; D007074:Immunoglobulin G / Q000097:blood*; D008297:Male; D008875:Middle Aged; D011187:Posture / Q000502:physiology; D011943:Receptors, Adrenergic, beta / Q000502:physiology*; D011976:Receptors, Muscarinic / Q000502:physiology*; D014664:Vasodilation / Q000502:physiology; D055815:Young Adult
chemical_list: D001323:Autoantibodies; D007074:Immunoglobulin G; D011943:Receptors, Adrenergic, beta; D011976:Receptors, Muscarinic