title: 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.
authors: L'UNAM Université Nantes Angers Le Mans, France; Oniris, "UPSP 5304 de physiopathologie animale et de pharmacologie fonctionnelle", Atlanpole-La Chantrerie, BP 40706, Nantes F-44307, France.
authors: M A
authors: MA
authors: Abdelkrim
authors: L'UNAM Université Nantes Angers Le Mans, France; Inserm UMR 1063, IBS-IRIS, rue des Capucins, F-49100 Angers, France.
authors: D
authors: D
authors: Leonetti
authors: L'UNAM Université Nantes Angers Le Mans, France; Oniris, "UPSP 5304 de physiopathologie animale et de pharmacologie fonctionnelle", Atlanpole-La Chantrerie, BP 40706, Nantes F-44307, France.
authors: E
authors: E
authors: Montaudon
authors: L'UNAM Université Nantes Angers Le Mans, France; Oniris, "Biotechnologie Pathologie Reproduction/RSB", Atlanpole-La Chantrerie, BP 40706, Nantes F-44307, France.
authors: G
authors: G
authors: Chatagnon
authors: L'UNAM Université Nantes Angers Le Mans, France; Oniris, "UPSP 5304 de physiopathologie animale et de pharmacologie fonctionnelle", Atlanpole-La Chantrerie, BP 40706, Nantes F-44307, France.
authors: M
authors: M
authors: Gogny
authors: L'UNAM Université Nantes Angers Le Mans, France; Oniris, "UPSP 5304 de physiopathologie animale et de pharmacologie fonctionnelle", Atlanpole-La Chantrerie, BP 40706, Nantes F-44307, France.
authors: J-C
authors: JC
authors: Desfontis
authors: L'UNAM Université Nantes Angers Le Mans, France; Inserm UMR 1063, IBS-IRIS, rue des Capucins, F-49100 Angers, France.
authors: J
authors: J
authors: Noireaud
authors: L'UNAM Université Nantes Angers Le Mans, France; Oniris, "UPSP 5304 de physiopathologie animale et de pharmacologie fonctionnelle", Atlanpole-La Chantrerie, BP 40706, Nantes F-44307, France. Electronic address: yassine.mallem@oniris-nantes.fr.
authors: M Y
authors: MY
authors: Mallem
mesh_terms: D000319:Adrenergic beta-Antagonists / Q000494:pharmacology; D000818:Animals; D000906:Antibodies / Q000494:pharmacology*; D001013:Aorta, Thoracic / Q000187:drug effects* / Q000502:physiology; D004730:Endothelium, Vascular / Q000187:drug effects; D007114:Immunization; D007074:Immunoglobulin G / Q000276:immunology; D008297:Male; D008638:Mesenteric Arteries / Q000187:drug effects* / Q000502:physiology; D010455:Peptides / Q000494:pharmacology*; D011487:Protein Conformation; D051381:Rats; D017208:Rats, Wistar; D018342:Receptors, Adrenergic, beta-1 / Q000737:chemistry / Q000276:immunology*; D014664:Vasodilation / Q000187:drug effects
chemical_list: D000319:Adrenergic beta-Antagonists; D000906:Antibodies; D007074:Immunoglobulin G; D010455:Peptides; D018342:Receptors, Adrenergic, beta-1
keywords: Autoantibody; Endothelium dysfunction; Heart failure; Immunization; Nitric oxide; β-Adrenoceptor