Effects of long-term active immunization with the second extracellular loop of human β1- or β3-adrenoceptors in thoracic aorta and mesenteric arteries in Lewis rats.
To evaluate whether active immunization producing β1- or β3-antibodies (β1-ABs and β3-ABs) detected in sera of patients with dilated cardiomyopathies has deleterious effects on vascular reactivity in Lewis rat thoracic aorta (TA) and small mesenteric arteries (SMA).



Lewis rats were immunized for 6months with peptidic sequences corresponding to the second extracellular loop of β1- and β3-adrenoceptors (ARs). During the immunization, systolic blood pressure (SBP) was monitored using the tail cuff method. The vascular reactivity of immunized rats was assessed by ex vivo studies on SMA and TA using various β-AR agonists, phenylephrine and KCl.



The immunizations producing functional β1-ABs and β3-ABs did not affect the SBP. However, in TA from β1-AR-immunized rats, the relaxations mediated by dobutamine and salbutamol were significantly impaired in comparison with adjuvant rats whereas nebivolol-induced relaxation was not modified. Moreover, phenylephrine and KCl-mediated contractions were enhanced in these rats. In contrast, immunization with β3-AR peptide led to the increase of relaxations induced by dobutamine in TA but did not change those induced by salbutamol and nebivolol. Surprisingly, in SMA from both rats immunized with β1- or β3-peptides, relaxations induced by the various β-agonists were not changed whereas phenylephrine and KCl-mediated contractions were impaired.



Our study shows that β1- and β3-ABs can affect vascular reactivity. β1-ABs would have a pathogenic action whereas β3-ABs would have a beneficial effect on aorta reactivity.
LUNAM University, Oniris, UPSP 5304 of Animal Pathophysiology and Functional Pharmacology, Atlanpôle La Chantrerie, BP 40706, 44307 Nantes, France.
E
E
Montaudon
LUNAM University, Oniris, INRA UMR U703, PanTHER, Atlanpôle La Chantrerie, BP 40706, 44307 Nantes, France.
L
L
Dubreil
LUNAM University, Oniris, UPSP 5304 of Animal Pathophysiology and Functional Pharmacology, Atlanpôle La Chantrerie, BP 40706, 44307 Nantes, France.
V
V
Lalanne
LUNAM University, INSERM, UMR 1087/CNRS 6291 Institut du Thorax, F44007 Nantes, France.
B
B
Jagu
LUNAM University, INSERM, UMR 1087/CNRS 6291 Institut du Thorax, F44007 Nantes, France.
G
G
Toumaniantz
LUNAM University, Oniris, UPSP 5304 of Animal Pathophysiology and Functional Pharmacology, Atlanpôle La Chantrerie, BP 40706, 44307 Nantes, France.
C
C
Thorin
LUNAM University, CNRS UMR 6214, INSERM U1083, F-49000 Angers, France.
D
D
Henrion
LUNAM University, Oniris, UPSP 5304 of Animal Pathophysiology and Functional Pharmacology, Atlanpôle La Chantrerie, BP 40706, 44307 Nantes, France.
J-C
JC
Desfontis
LUNAM Univsersity, Oniris, UPSP, Sanitary Safety in Biotechnologies of the Reproduction, La Chantrerie, BP 40706, 44307 Nantes, France.
L
L
Martignat
LUNAM University, Oniris, UPSP 5304 of Animal Pathophysiology and Functional Pharmacology, Atlanpôle La Chantrerie, BP 40706, 44307 Nantes, France. Electronic address: yassine.mallem@oniris-nantes.fr.
M Y
MY
Mallem
D000318:Adrenergic beta-Agonists / Q000494:pharmacology; D000818:Animals; D001013:Aorta, Thoracic / Q000276:immunology / Q000378:metabolism; D001323:Autoantibodies / Q000276:immunology*; D008297:Male; D008638:Mesenteric Arteries / Q000276:immunology / Q000378:metabolism; D010455:Peptides / Q000008:administration & dosage / Q000276:immunology; D010656:Phenylephrine / Q000494:pharmacology; D011189:Potassium Chloride / Q000494:pharmacology; D051381:Rats; D011917:Rats, Inbred Lew; D018342:Receptors, Adrenergic, beta-1 / Q000276:immunology* / Q000378:metabolism; D022702:Receptors, Adrenergic, beta-3 / Q000276:immunology* / Q000378:metabolism; D014611:Vaccination / Q000379:methods*
D000318:Adrenergic beta-Agonists; D001323:Autoantibodies; D010455:Peptides; D018342:Receptors, Adrenergic, beta-1; D022702:Receptors, Adrenergic, beta-3; D010656:Phenylephrine; D011189:Potassium Chloride
Aorta; Auto-antibodies; Mesenteric artery; Rats; Vascular reactivity; β-Adrenoceptor