Autoantibody activation of beta-adrenergic and muscarinic receptors contributes to an "autoimmune" orthostatic hypotension

J Am Soc Hypertens. Jan-Feb 2012;6(1):40-7. doi: 10.1016/j.jash.2011.10.003. Epub 2011 Nov 30.

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.

Conclusion: 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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Aged
  • Autoantibodies / blood*
  • Case-Control Studies
  • Female
  • Humans
  • Hypotension, Orthostatic / blood
  • Hypotension, Orthostatic / immunology*
  • Hypotension, Orthostatic / physiopathology*
  • Immunoglobulin G / blood*
  • Male
  • Middle Aged
  • Posture / physiology
  • Receptors, Adrenergic, beta / physiology*
  • Receptors, Muscarinic / physiology*
  • Vasodilation / physiology
  • Young Adult

Substances

  • Autoantibodies
  • Immunoglobulin G
  • Receptors, Adrenergic, beta
  • Receptors, Muscarinic