[Antibodies against the second extracellular loop of beta1-adrenergic receptor induce aortic endothelial dysfunction in Wistar rat].
OBJECTIVE
To evaluate the effect of active immunization with a peptide corresponding to the second extracellular loop of the human beta1-adrenoceptors (β(1)-AR) on the reactivity of Wistar rat isolated aorta.


METHODS
Nine-week-old Wistar rats were actively immunized for 3months with a peptide corresponding to the second extracellular loop of the human β(1)-AR. Specific immunoglobulins G (IgG) were characterized by Elisa and the bicinchonic acid protein assay and their functionality were tested in isolated ventricular cardiomyocytes (IVC) from control rats. Aortic rings isolated from control or immunized rats were mounted in organ baths. Then, contractile curves to phenylephrine (1nM to 300μM) and relaxant curves to acetylcholine (1nM to 100μM) and isoprenaline (1nM to 30μM) were established.


RESULTS
Cell shortening increased dose-dependently in rat IVC superfused with IgG containing β(1)-AR antibodies (10 or 25μg/mL). Isoprenaline-induced positive inotropy was strongly reduced in IgG containing β(1)-AR antibodies preincubated (3h) IVC. Phenylephrine-and acetylcholine-induced aortic responses were greatly inhibited in immunized rats compared to control ones. However, active immunization did not influence the isoprenaline-mediated relaxation.


CONCLUSIONS
The present work confirms that β(1)-AR antibodies directed against the second extracellular loop of β(1)-AR induce a positive inotropic effect in adult rat IVC. Moreover, we demonstrated, for the first time, that 3-month immunization with β(1)-AR peptide was associated with altered aortic endothelial function without change in the β-AR-mediated vasorelaxation.
UPSP 5304 de physiopathologie animale et pharmacologie fonctionnelle, LUNAM université, Oniris, Atlanpole La Chantrerie, BP 40706, 44307 Nantes, France.
M A
MA
Abdelkrim
J
J
Noireaud
G
G
Chatagnon
M
M
Gogny
J-C
JC
Desfontis
M Y
MY
Mallem
D000109:Acetylcholine / Q000494:pharmacology; D000318:Adrenergic beta-Agonists / Q000494:pharmacology; D000465:Algorithms; D000818:Animals; D001011:Aorta / Q000187:drug effects; D001323:Autoantibodies / Q000276:immunology*; D003196:Computer Graphics; D004195:Disease Models, Animal; D004730:Endothelium, Vascular / Q000187:drug effects; D006801:Humans; D007074:Immunoglobulin G / Q000097:blood*; D066298:In Vitro Techniques; D007545:Isoproterenol / Q000494:pharmacology; D008297:Male; D032383:Myocytes, Cardiac / Q000187:drug effects; D010656:Phenylephrine / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D018342:Receptors, Adrenergic, beta-1 / Q000276:immunology*; D014662:Vasoconstrictor Agents / Q000494:pharmacology; D014665:Vasodilator Agents / Q000494:pharmacology
D000318:Adrenergic beta-Agonists; D001323:Autoantibodies; D007074:Immunoglobulin G; D018342:Receptors, Adrenergic, beta-1; D014662:Vasoconstrictor Agents; D014665:Vasodilator Agents; D010656:Phenylephrine; D007545:Isoproterenol; D000109:Acetylcholine