title: Some components of the cardiac β-adrenergic system are altered in the chronic indeterminate form of experimental Trypanosoma cruzi infection.
abstract: 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 β-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 β-adrenergic receptors' (β-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 β-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 β-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 β-adrenergic system at different levels: (i) between catecholamines and the β(1)-receptors; (ii) between the receptors' activation and the adenylyl-cyclase activation; and/or (iii) between cAMP and the contractile response.
authors.affiliation: Cátedra de Física Biomédica, Facultad de Ciencias Médicas, Universidad Nacional de Córdoba, Santa Rosa 1085, PC 5000 Córdoba, Argentina.
authors.forename: M
authors.initials: M
authors.lastname: Silvina Lo Presti
authors.forename: H
authors.initials: H
authors.lastname: Walter Rivarola
authors.forename: Juan Manuel
authors.initials: JM
authors.lastname: Bustamante
authors.forename: Alicia R
authors.initials: AR
authors.lastname: Fernández
authors.forename: Julio E
authors.initials: JE
authors.lastname: Enders
authors.forename: Gloria
authors.initials: G
authors.lastname: Levin
authors.forename: Ernesto
authors.initials: E
authors.lastname: Juaneda
authors.forename: Ricardo
authors.initials: R
authors.lastname: Fretes
authors.forename: M
authors.initials: M
authors.lastname: Fernanda Triquell
authors.forename: Patricia A
authors.initials: PA
authors.lastname: Paglini-Oliva
mesh_terms: D000818:Animals; D002598:Chagas Cardiomyopathy / Q000378:metabolism* / Q000469:parasitology / Q000503:physiopathology; D000242:Cyclic AMP / Q000378:metabolism; D004562:Electrocardiography; D004837:Epinephrine / Q000378:metabolism; D006321:Heart / Q000469:parasitology / Q000503:physiopathology; D006801:Humans; D051379:Mice; D009200:Myocardial Contraction; D009206:Myocardium / Q000378:metabolism; D009638:Norepinephrine / Q000378:metabolism; D011943:Receptors, Adrenergic, beta / Q000378:metabolism*; D015398:Signal Transduction; D014349:Trypanosoma cruzi / Q000502:physiology*
chemical_list: D011943:Receptors, Adrenergic, beta; D000242:Cyclic AMP; D009638:Norepinephrine; D004837:Epinephrine