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Antibodies against the second extracellular loop of β1-adrenergic receptors induce endothelial dysfunction in conductance and resistance arteries of the Wistar rat

Abstract :

Autoantibodies against β1-adrenoceptors (β1-ARs) have been detected in the serum of patients with various cardiac diseases; however, the pathological impact of these autoantibodies (β1-AABs) has only been evaluated in cardiac tissue. The purpose of the present study was to evaluate whether β1-AABs have deleterious effects on vascular reactivity in rats.

An enzyme-linked immunosorbent assay was used to detect β1-AABs in sera from immunized rats over a period of 1–3 months using the peptidic sequence of the second extracellular loop of human β1-AR. Functional studies were performed in thoracic aortic (TA) and small mesenteric artery (SMA) rings from immunized rats. Following pre-contraction with phenylephrine (0.3 μM and 3 μM for the TA and SMA respectively), cumulative concentration–response curves (CCRCs) to various β-AR agonists (isoproterenol, dobutamine, salbutamol, SR 58611A), acetylcholine, A23187, and sodium nitroprusside (SNP) were then plotted.

The relaxations induced by dobutamine, SR 58611A, and acetylcholine were significantly impaired, but salbutamol-induced relaxations were not affected, in both vessels from immunized rats. A significant impairment of isoproterenol-induced relaxation was only observed in SMA. CCRCs to SNP were not modified in either of the vessels. A23187-induced relaxation was impaired in immunized rats. Following pretreatment with l-arginine, vasorelaxation to acetylcholine and SR 58611A was restored in immunized rats.

This study demonstrates that immunization against the second extracellular loop of β1-ARs has a deleterious impact on vasorelaxations in the TA and SMA of rats, involving alterations in endothelium-dependent NO signaling pathways.

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https://hal.univ-angers.fr/hal-03276620
Contributeur : Okina Université d'Angers <>
Soumis le : vendredi 2 juillet 2021 - 11:43:45
Dernière modification le : samedi 3 juillet 2021 - 03:08:22

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Mohammed Abdelkrim, Daniela Leonetti, E. Montaudon, Gérard Chatagnon, M. Gogny, et al.. Antibodies against the second extracellular loop of β1-adrenergic receptors induce endothelial dysfunction in conductance and resistance arteries of the Wistar rat. International Immunopharmacology, Elsevier, 2014, 19 (2), pp.308-316. ⟨10.1016/j.intimp.2014.01.029⟩. ⟨hal-03276620⟩

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