Coimmunization with α1- and β1-adrenergic receptor peptides induced postural tachycardia in rabbits, which was suppressed by antibody-neutralizing peptides at 6 and 30 weeks.
Demonstrates that α1- and β1-adrenergic receptor autoantibodies induce postural tachycardia in a rabbit model, which can be reversed with neutralizing peptides, supporting an autoimmune mechanism for POTS.
Background Previous studies have demonstrated that functional autoantibodies to adrenergic receptors may be involved in the pathogenesis of postural tachycardia syndrome. The objective of this study was to examine the impact of these autoantibodies on cardiovascular responses to postural changes and adrenergic orthosteric ligand infusions in immunized rabbits. Methods and Results Eight New Zealand white rabbits were coimmunized with peptides from the α1-adrenergic receptor and β1-adrenergic receptor (β1AR). Tilt test and separate adrenergic agonist infusion studies were performed on conscious animals before and after immunization and subsequent treatment with epitope-mimetic peptide inhibitors. At 6 weeks after immunization, there was a greater percent increase in heart rate upon tilting compared with preimmune baseline. No significant difference in blood pressure response to tilting was observed. The heart rate response to infusion of the β-adrenoceptor agonist isoproterenol was significantly enhanced in immunized animals, suggesting a positive allosteric effect of β1AR antibodies. In contrast, the blood pressure response to infusion of the α1-adrenergic receptor agonist phenylephrine was attenuated in immunized animals, indicating a negative allosteric effect of α1-adrenergic receptor antibodies. Injections of antibody-neutralizing peptides suppressed the postural tachycardia and reversed the altered heart rate and blood pressure responses to orthosteric ligand infusions in immunized animals at 6 and 30 weeks. Antibody production and suppression were confirmed with in vitro bioassays. Conclusions The differential allosteric effect of α1-adrenergic receptor and β1AR autoantibodies would lead to a hyperadrenergic state and overstimulation of cardiac β1AR. These data support evidence for an autoimmune basis for postural tachycardia syndrome.
Li et al. (Tue,) conducted a other in Postural tachycardia syndrome (n=8). Coimmunization with α1-adrenergic and β1-adrenergic receptor peptides and subsequent epitope-mimetic peptide inhibitors vs. Preimmune baseline was evaluated on Heart rate and blood pressure responses to postural changes (tilt test) and adrenergic orthosteric ligand infusions. Coimmunization with α1- and β1-adrenergic receptor peptides induced postural tachycardia in rabbits, which was suppressed by antibody-neutralizing peptides at 6 and 30 weeks.