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

• We evaluate the effect of β1-adrenergic autoantibodies upon the rat aorta and mesenteric artery reactivity.
• β1-Adrenergic autoantibodies alter β1- and β3-adrenocepror-mediated relaxations
• β1-Adrenergic autoantibodies also alter relaxation to acetylcholine.
• β2-Adrenocepror-mediated relaxation was unaltered by β1-adrenergic autoantibodies.
• β1-Adrenergic autoantibodies did not modify the relaxation to sodium nitroprusside.

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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