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

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

Author information

1
Heart Rhythm Institute, University of Oklahoma Health Sciences Center and VA Medical Center, Oklahoma City, OK, USA.

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.

PMID:
22130180
PMCID:
PMC3259269
DOI:
10.1016/j.jash.2011.10.003
[Indexed for MEDLINE]
Free PMC Article

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