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

M S LO PRESTI; H W RIVAROLA; J M BUSTAMANTE; A R FERNANDEZ; J E ENDERS; G LEVIN; E JUANEDA; R FRETES; M F TRIQUELL; P A PAGLINI-OLIVA

INTERNATIONAL JOURNAL OF PARASITOLOGY

ELSEVIER

Año: 2008 vol. 38 p. 1481 - 1492

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.Westudied some components of the cardiac b-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 b-adrenergic receptors’ (b-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 b-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 b-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 badrenergic system at different levels: (i) between catecholamines and the b1-receptors; (ii) between the receptors’ activation and the adenylyl-cyclase activation; and/or (iii) between cAMP and the contractile response.