6533b829fe1ef96bd128add4

RESEARCH PRODUCT

0149: Agonistic anti β3-adrenoceptor antibodies do not affect the β1-adrenoceptor-mediated inotropy and the β3 adrenoceptor-mediated vasorelaxation in Lewis rat

subject

description

Cardiac activity of autoantibodies (AABs) directed against β1-adrenoceptor (β1-AR) has been proposed to play an important role in the pathogenesis of dilated cardiomyopathy. Our previous work has shown that the immunization of rats with the second extracellular loop (ECII) of β1-AR induced endothelial dysfunction in aorta and mesenteric arteries. However, until now, no study has explored the cardiovascular effects of β3-AABs alone or combined with β1-AABs.AimTo evaluate whether β3-AABs possess β3-AR agonistic effect and whether active immunization producing β3-AABs and/or β1-AABs has deleterious effects on cardiac and vascular reactivity in Lewis rats.MethodsLewis rats were immunized for 3 months with peptidic sequences corresponding to the ECII of β3-AR and/or β1-AR.? The agonistic effect of β3-AABs was evaluated on electrically field-stimulated isolated cardiomyocytes from adult rabbit by measuring the cell shortening. Inotropy studies and isolated aorta and mesenteric artery studies were also conducted on immunized rats.ResultsSR58611A (10nM), a preferential β3-AR agonist and purified β3-AABs (25μg/mL) induced a decrease of cell shortening (–39.6±4.4% (n=11) and –18.5±3.9% (n=10) respectively). This decrease was significantly inhibited when the cardiomyocytes were preincubated with the L-748337 (1μM), a selective β3-AR antagonist (p<0.05). The cell shortening of cardiomyocytes from rats immunized against the β1-AR, in response to isoprenaline (10nM), was significantly decreased (p<0.05). In contrast, this effect was conserved in rats immunized against β3-AR or β3/β1-AR. Vasorelaxations induced by acetylcholine and SR58611A in both aorta and mesenteric arteries were unaltered by immunization.These results show that β3-AABs induced a β3-AR agonist-like activity. They would not have a cardiovascular pathogenic action but would offset the cardiac and endothelial dysfunctions caused by β1-AABs.