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

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.