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 β 1 - or β 3 -antibodies (β 1 -ABs and β 3 -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 6 months with peptidic sequences corresponding to the second extracellular loop of β 1 - and β 3 -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 β 1 -ABs and β 3 -ABs did not affect the SBP. However, in TA from β 1 -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 β 3 -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 β 1 - or β 3 -peptides, relaxations induced by the various β-agonists were not changed whereas phenylephrine and KCl-mediated contractions were impaired. Conclusions Our study shows that β 1 - and β 3 -ABs can affect vascular reactivity. β 1 -ABs would have a pathogenic action whereas β 3 -ABs would have a beneficial effect on aorta reactivity.