The Beta Adrenergic system in acute and indeterminate Chagas disease

LO PRESTI, M; BUSTAMANTE, J; RIVAROLA, W; FERNANDEZ, A; ENDERS, J; LEVIN, G; PAGLINI, P

Florencia, Italia

Congreso; 7th European Congress of Chemotherapy and Infection; 2005

Federation of the European Societies for Chemotherapy and for Infection

Chagas’ disease is one of the most important determinants of congestive heart failure and sudden death in Latin America. It is caused by the protozoan parasite Trypanosoma cruzi and it is characterized in humans by irreversible lesions of the cardiac muscle and the autonomic nervous system. The beta-adrenergic receptor (beta-AR) pathway is the most powerful tool by which heart rate and contractility are physiologically regulated and maintained and participates in the homeostatic regulation of the cardiovascular system. This becomes particularly important in Chagas’ disease for which it is possible to consider that the beta-adrenergic signal transduction system would be altered in mice hearts infected with T. cruzi in different degree depending on the infection stage and the infecting parasite strain. In the present work we studied some representative components of the beta-adrenergic signal transduction system in mice hearts infected with T. cruzi Tulahuen strain and with the SGO Z12 isolate, in the acute and the indeterminate stages of Chagas disease. We determined: the primary messenger (epinephrine and norepinephrine) levels in plasma by RF-HPLC; the cardiac beta-receptor density and affinity by binding with trited dihidroalprenolol; the cardiac concentration of the second messenger (cAMP) (by ELISA) given its importance for the activation of PKA and the consequent phosphorylation of the proteins involved in cardiac contraction; and the cardiac contractility and functional studies of the beta-ARs as a response to the ligand binding to the receptor. In the acute phase, the plasma catecholamines levels were diminished in both infected groups when compared to the uninfected one (p<0.01). In the indeterminate stage, on the other hand, both epinephrine and norepineprine were significantly higher in the SGO Z12 infected group (p<0.05) while they remained within normal values in the Tulahuen infected animals. The receptor’s affinity was diminished in both stages (p<0.05) while their density was higher only in the SGO-Z12 infected one (p<0.01). The cAMP levels augmented with the evolution of the infection in both infected groups (p<0.01); the basal contractile force, however, remained unchanged,  while the response to exogenous catecholamines increased only in the Tulahuen group, even though the SGO Z12 had higher cardiac cAMP levels (p<0.01). Our results reveal a clear differentiation in the alterations produced by different T. cruzi strains that could point out to a probable differential alteration in the signaling pathway. Biochemical and molecular diversity between parasite strains could produce the different pathological development of the T. cruzi infection. Taking together, these results point to demonstrate that different parasite strains determine different alterations in the cardiac beta-adrenergic pathway and that they take place from the early acute phase and maintain through the indeterminate stage of Chagas’ disease, proving that this last stage is not as silent as it is thought to be, presenting alterations that probably determine the beggining of the chronic myocardiopathy caracteristic of the disease.