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

Abstract

Objective: 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).

Design and method: 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.

Results: 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.

Conclusions: 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.

Keywords: Aorta; Auto-antibodies; Mesenteric artery; Rats; Vascular reactivity; β-Adrenoceptor.