© 1999 by European Society of Cardiology
Copyright © 1999, European Society of Cardiology
Alterations in cardiac beta-adrenergic receptors in chagasic mice and their association with circulating beta-adrenoceptor-related autoantibodies
Centro de Estudios Farmacológicos y Botánicos (CEFYBO), Consejo Nacional de Investigaciones Cient
éficas y Técnicas de la República Argentina (CONICET) and School of Medicine and Dentistry, University of Buenos Aires, Buenos Aires, Argentina
* Corresponding author. CEFYBO-CONICET, Serrano 669-5to. Piso, 1414 Buenos Aires, Argentina. Tel.: +54-1-855-7194; fax: +54-1-856-2751.
Objetive: Cardiac tissue from chagasic mice was studied to evaluate the expression and biological activity of β-adrenoceptors in association with circulating β-adrenoceptor-related autoantibodies. Methods: BALB/c inbred mice that were either treated or not treated with atenolol (2.5 mg/kg) and infected or not infected with 1x104 trypomastigotes (CA-1 strain) were sacrificed weekly up to week nine. Morphological, binding and contractility studies were performed on the four different groups of animals. The effect of their serum antibodies was also assayed in binding and contractility studies on normal heart preparations. Results: Hearts from chagasic myocarditis mice showed a β-adrenoceptor-related dysfunction, with a decrease in heart contractility, impaired response to exogenous β-adrenoceptor agonist and a significant reduction in β-adrenergic binding sites. Those effects were maximum at eight–nine weeks post-infection and were improved by treating infected mice with atenolol. In addition, serum or IgG from chagasic myocarditis mice was capable of interacting with cardiac β-adrenoceptors, reducing the number of binding sites and inhibiting the contractile response to exogenous norepinephrine. IgG effects that were observed in normal myocardium, were highest in sera from mice eight–nine weeks post-infection and correlate with the degree of myocarditis. Moreover, chagasic autoantibodies from infected mice recognized a peptide corresponding to the sequence of the second extracellular loop of the human β1-adrenoceptor. Conclusions: (1) The development of alterations in β-adrenergic receptors, related to cardiac dysfunction, may be associated with the presence of circulating antibodies against these receptors and (2) it is possible that the chronic deposits of these autoantibodies in cardiac β-adrenoceptors could lead to a progressive blockade with sympathetic denervation, a phenomenon that has been described in the course of chagasic myocarditis.
KEYWORDS Chagasic myocarditis; β-Adrenoceptors; Antiheart antibodies; Cardiac dysfunction; Anti-adrenoceptor antibodies