title: [Cardiovascular effects of beta1 and beta3-adrenergic receptor autoantibodies in Lewis rat].
abstract: OBJECTIVE
  To analyze vascular reactivity changes in response to immunization protocols with antigens corresponding to the second extracellular loop of -β3 and -β1 and 3 adrenergic receptors (AR).
  
  
  METHODS
  Lewis rats were immunized for 3months with peptidic sequences corresponding to the second extracellular loop of β3-AR or β1 and 3-AR. Specific β3-AR antibodies were characterized by Elisa and purified using "Proteus Protein G" kit. Their functionality were tested in rabbit isolated ventricular cardiomyocytes. Aortic and mesenteric artery rings isolated from control or immunized rats were mounted in organ baths and precontracted with phenylephrine. Then, relaxant curves were established.
  
  
  RESULTS
  SR58611A (10nM), a preferential β3-AR agonist and purified β3-AR antibodies (25μg/mL) induced a decrease of cell shortening (-39.56±4.4% [n=11] and -18.45±3.9% [n=10] respectively) in isolated cardiomyocytes. This decrease was significantly inhibited when the cardiomyocytes were pre-incubated with the L-748337 (1μM), a selective β3-AR antagonist (P<0.05). In contrast with what was observed in rats immunized against the β1-AR, vasorelaxations induced by acetylcholine and SR58611A in both aorta and mesenteric arteries were unaltered in rats immunized against the β3-AR and β1 and 3-AR.
  
  
  CONCLUSIONS
  These results show, for the first time, that β3-AR antibodies induced a β3-AR agonist-like activity. They would not have a vascular pathogenic action but would offset the endothelial dysfunction caused by β1-AR antibodies.
authors.affiliation: LUNAM université, Oniris, « UPSP 5304 de physiopathologie animale et pharmacologie fonctionnelle », Atlanpole La Chantrerie, BP 40706, 44307 Nantes, France. Electronic address: elodie.montaudon@oniris-nantes.fr.
authors.forename: E
authors.initials: E
authors.lastname: Montaudon
authors.affiliation: LUNAM université, Oniris, « UPSP 5304 de physiopathologie animale et pharmacologie fonctionnelle », Atlanpole La Chantrerie, BP 40706, 44307 Nantes, France.
authors.forename: M A
authors.initials: MA
authors.lastname: Abdelkrim
authors.affiliation: LUNAM université, Oniris, « UPSP 5304 de physiopathologie animale et pharmacologie fonctionnelle », Atlanpole La Chantrerie, BP 40706, 44307 Nantes, France.
authors.forename: J-C
authors.initials: JC
authors.lastname: Desfontis
authors.affiliation: LUNAM université, Oniris, « UPSP 5304 de physiopathologie animale et pharmacologie fonctionnelle », Atlanpole La Chantrerie, BP 40706, 44307 Nantes, France. Electronic address: yassine.mallem@oniris-nantes.fr.
authors.forename: M Y
authors.initials: MY
authors.lastname: Mallem
mesh_terms: D058673:Adrenergic beta-3 Receptor Antagonists / Q000494:pharmacology*; D000318:Adrenergic beta-Agonists / Q000494:pharmacology*; D000818:Animals; D001011:Aorta / Q000187:drug effects; D001323:Autoantibodies / Q000276:immunology*; D004195:Disease Models, Animal; D004730:Endothelium, Vascular / Q000187:drug effects*; D007114:Immunization / Q000379:methods; D066298:In Vitro Techniques; D008297:Male; D032383:Myocytes, Cardiac / Q000187:drug effects*; D011817:Rabbits; D051381:Rats; D011917:Rats, Inbred Lew; D018342:Receptors, Adrenergic, beta-1 / Q000276:immunology*; D022702:Receptors, Adrenergic, beta-3 / Q000276:immunology*
chemical_list: D058673:Adrenergic beta-3 Receptor Antagonists; D000318:Adrenergic beta-Agonists; D001323:Autoantibodies; D018342:Receptors, Adrenergic, beta-1; D022702:Receptors, Adrenergic, beta-3
keywords: Auto-anticorps; Autoantibodies; Endothelium; Endothélium; Rat; Réactivité vasculaire; Récepteur adrénergique β; Vascular reactivity; β adrenoceptor