scholarly journals Activating autoantibodies to the β1/2-adrenergic and M2 muscarinic receptors associate with atrial tachyarrhythmias in patients with hyperthyroidism

Endocrine ◽  
2014 ◽  
Vol 49 (2) ◽  
pp. 457-463 ◽  
Author(s):  
Allison Galloway ◽  
Hongliang Li ◽  
Megan Vanderlinde-Wood ◽  
Muneer Khan ◽  
Alexandria Benbrook ◽  
...  
Keyword(s):  
Muscarinic Receptors ◽  
Atrial Tachyarrhythmias ◽  
Activating Autoantibodies ◽  
M2 Muscarinic Receptors

scholarly journals β1-Adrenergic and M2 Muscarinic Autoantibodies and Thyroid Hormone Facilitate Induction of Atrial Fibrillation in Male Rabbits

Endocrinology ◽  
2016 ◽  
Vol 157 (1) ◽  
pp. 16-22 ◽  
Author(s):  
Hongliang Li ◽  
Taylor Murphy ◽  
Ling Zhang ◽  
Bing Huang ◽  
Vineet Veitla ◽  
...  
Keyword(s):  
Atrial Fibrillation ◽  
Thyroid Hormone ◽  
Muscarinic Receptors ◽  
Refractory Period ◽  
Electrophysiological Study ◽  
Subsequent Treatment ◽  
Effective Refractory Period ◽  
Activating Autoantibodies ◽  
The Impact ◽  
M2 Muscarinic Receptors

Abstract Activating autoantibodies to the β1-adrenergic and M2 muscarinic receptors are present in a very high percentage of patients with Graves' disease and atrial fibrillation (AF). The objective of this study was to develop a reproducible animal model and thereby to examine the impact of these endocrine-like autoantibodies alone and with thyroid hormone on induction of thyroid-associated atrial tachyarrhythmias. Five New Zealand white rabbits were coimmunized with peptides from the second extracellular loops of the β1-adrenergic and M2 muscarinic receptors to produce both sympathomimetic and parasympathomimetic antibodies. A catheter-based electrophysiological study was performed on anesthetized rabbits before and after immunization and subsequent treatment with thyroid hormone. Antibody expression facilitated the induction of sustained sinus, junctional and atrial tachycardias, but not AF. Addition of excessive thyroid hormone resulted in induced sustained AF in all animals. AF induction was blocked acutely by the neutralization of these antibodies with immunogenic peptides despite continued hyperthyroidism. The measured atrial effective refractory period as one parameter of AF propensity shortened significantly after immunization and was acutely reversed by peptide neutralization. No further decrease in the effective refractory period was observed after the addition of thyroid hormone, suggesting other cardiac effects of thyroid hormone may contribute to its role in AF induction. This study demonstrates autonomic autoantibodies and thyroid hormone potentiate the vulnerability of the heart to AF, which can be reversed by decoy peptide therapy. These data help fulfill Witebsky's postulates for an increased autoimmune/endocrine basis for Graves' hyperthyroidism and AF.

Dysfunction of M2-muscarinic receptors in pulmonary parasympathetic nerves after antigen challenge

1991 ◽  
Vol 71 (6) ◽  
pp. 2255-2261 ◽  
Author(s):  
A. D. Fryer ◽  
M. Wills-Karp
Keyword(s):  
Muscarinic Receptors ◽  
Guinea Pigs ◽  
Antigen Challenge ◽  
Saline Control ◽  
Control Group ◽  
Vagus Nerves ◽  
Parasympathetic Nerves ◽  
Volume Blood ◽  
M2 Muscarinic Receptors ◽  
Stimulation Of

The effect of antigen challenge on the function of neuronal M2-muscarinic autoreceptors in the lungs was studied in anesthetized guinea pigs. Guinea pigs were injected intraperitoneally with saline (control group) or ovalbumin (10 mg/kg) on days 1, 3, and 5. One group of sensitized animals was challenged on days 20–25 with aerosolized ovalbumin for 5 min/day (challenged group), while another group of the sensitized animals was not challenged (sensitized group). On day 26 the animals were anesthetized, paralyzed, tracheostomized, and artificially ventilated. Pulmonary inflation pressure (Ppi), tidal volume, blood pressure, and heart rate were recorded. Both vagus nerves were cut, and electrical stimulation of the distal portions caused bronchoconstriction (measured as an increase in Ppi) and bradycardia. In the control group, pilocarpine (1–100 micrograms/kg iv) attenuated vagally induced bronchoconstriction by stimulating inhibitory M2-muscarinic receptors on parasympathetic nerves in the lungs. Conversely, blockade of these receptors with the antagonist gallamine (0.1–10 mg/kg iv) produced a marked potentiation of vagally induced bronchoconstriction. These results confirm previous findings. In the challenged guinea pigs, pilocarpine did not inhibit vagally induced bronchoconstriction. Furthermore, gallamine did not potentiate vagally induced bronchoconstriction to the same degree as in the controls. In the group of animals that was sensitized but not challenged, the potentiation of vagally induced bronchoconstriction by gallamine was identical to the controls. There was no increase in baseline Ppi in the sensitized or challenged animals compared with the controls.(ABSTRACT TRUNCATED AT 250 WORDS)

Involvement of M2 muscarinic receptors in relaxant response of circular muscle of mouse gastric antrum.

2006 ◽  
Vol 18 (3) ◽  
pp. 226-233 ◽  
Author(s):  
t. takeuchi ◽  
m. toyoshima ◽  
k. mukai ◽  
k. hagi ◽  
m. matsui ◽  
...  
Keyword(s):  
Muscarinic Receptors ◽  
Circular Muscle ◽  
Gastric Antrum ◽  
Relaxant Response ◽  
M2 Muscarinic Receptors

Multiple Autoantibodies against Cardiovascular Receptors as Biomarkers in Hypertensive Heart Disease

Cardiology ◽  
2019 ◽  
Vol 142 (1) ◽  
pp. 47-55 ◽  
Author(s):  
Xin Wang ◽  
Yuan Zhang ◽  
Juan Zhang ◽  
Yu-Xing Wang ◽  
Xiao-Rong Xu ◽  
...  
Keyword(s):  
Heart Disease ◽  
Angiotensin Ii ◽  
Muscarinic Receptors ◽  
Hypertensive Heart Disease ◽  
Left Ventricular ◽  
Left Ventricular Ejection ◽  
Enzyme Linked Immunosorbent Assay ◽  
Ventricular Ejection Fraction ◽  
M2 Muscarinic Receptors ◽  
Normal Controls

Objectives: The pathogenesis of hypertensive heart disease (HHD) remains unclear, which might include autoimmunity. The aim of the present study was to determine whether a relationship exists between the presence of autoantibodies against β1, β2, α1 adrenoreceptors, M2-muscarinic receptors, angiotensin II type1 receptors and HHD. Methods: In the present study, 44 patients diagnosed with HHD, 36 patients with hypertension, and 40 controls were also enrolled. The measurement of these 5 autoantibodies was performed by enzyme-linked immunosorbent assay. Results: The frequencies of autoantibodies against β1, β2, α1 adrenoreceptors, autoantibodies against M2-muscarinic receptors and autoantibodies against angiotensin II type1 receptors were significantly higher in patients with HHD, when compared to patients with hypertension and normal controls (all p < 0.001). In addition, the titers of these 5 autoantibodies significantly increased in patients with HHD. Patients who were positive for all 5 autoantibodies had larger left ventricular end-diastolic diameter (60.5 ± 4.9 vs. 57.8 ± 5.0 vs. 52.5 ± 5.3 mm) and worse left ventricular ejection fraction (45.0 ± 11.0 vs. 56.6 ± 10.4 vs. 57.8 ± 5.3%), when compared to patients not positive for all the 5 autoantibodies and patients negative for all the 5 autoantibodies (χ2 = 9.524, p = 0.009 and χ2 = 7.689, p = 0.021). Furthermore, a significant positive correlation was observed between each 2 autoantibodies of these 5 autoantibodies (all p < 0.001). Conclusion: Multiple autoantibodies of cardiovascular receptors may be involved in the pathogenesis and may be predictive factors of HHD.

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