Some components of the cardiac beta-adrenergic system are altered in the chronic indeterminate form of the experimental Trypanosoma cruzi infection

LO PRESTI, M. SILVINA; RIVAROLA, H. WALTER; BUSTAMANTE, JUAN MANUEL; FERNANDEZ, ALICIA R; ENDERS, JULIO E; LEVIN, GLORIA; JUANEDA, ERNESTO; FRETES, RICARDO; TRIQUELL, M. FERNANDA; PAGLINI-OLIVA, PATRICIA A.

INTERNATIONAL JOURNAL FOR PARASITOLOGY

Elsevier

Año: 2008

0020-7519

The chronic indeterminate form of Trypanosoma cruzi infection could be the key to knowing which patients will develop chagasic myocardiopathy. Infected mice present a period in which cardiac functional and structural alterations are different from those described for acute or chronic phases.We studied some components of the cardiac beta-adrenergic system in mouse hearts infected with T. cruzi Tulahuen strain or SGO-Z12 isolate during the chronic indeterminate phase of infection. We determined: (i) the primary messenger (epinephrine and norepinephrine) levels in plasma by reverse-phase-HPLC; (ii) the cardiac beta-adrenergic receptors’ (beta-AR) density and affinity by binding with tritiated dihidroalprenolol and by immunofluorescence; (iii) the cardiac concentration of the second messenger (cAMP) (by ELISA) given its importance for the phosphorylation of the proteins involved in cardiac contraction; (iv) the cardiac contractility and functional studies of the beta-ARs as a response to the ligand binding to the receptor; and (v) the left ventricular ejection fraction as a measure of in vivo cardiac function. Plasma catecholamines levels remained similar to those found in uninfected controls. The beta-ARs’ affinity decreased in both infected groups compared with the uninfected group (P < 0.05) while the receptors’ density increased only in the SGO-Z12 group (P < 0.01). Cyclic AMP levels were higher in both infected groups (P < 0.01) relative to controls, and were higher in SGO-Z12-infected mice compared with those infected with the Tulahuen strain. However, the basal contractile force remained unchanged and the response to catecholamines only increased in the Tulahuen group (P < 0.05). The left ventricular ejection fraction, on the other hand, was diminished in SGO-Z12-infected mice. Heterogeneity between T. cruzi strains determine, in the chronic indeterminate form, alterations in the signaling pathways of the beta-adrenergic system at different levels: (i) between catecholamines and the beta1-receptors; (ii) between the receptors’ activation and the adenylyl-cyclase activation; and/or (iii) between cAMP and the contractile response.