Hostname: page-component-78c5997874-v9fdk Total loading time: 0 Render date: 2024-11-19T11:32:37.200Z Has data issue: false hasContentIssue false
  • English
  • Français

Characterization of cardiopulmonary function and cardiac muscarinic and adrenergic receptor density adaptation in C57BL/6 mice with chronic Trypanosoma cruzi infection

Published online by Cambridge University Press:  18 September 2006

N. N. ROCHA ,
S. GARCIA ,
L. E. D. GIMÉNEZ ,
C. C. Q. HERNÁNDEZ ,
J. F. V. SENRA ,
R. S. LIMA ,
F. CYRINO ,
E. BOUSKELA ,
M. B. P. SOARES  and
R. RIBEIRO DOS SANTOS
...Show all authors
N. N. ROCHA
Affiliation:
Instituto de Biofísica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil Universidade Federal Fluminense, Niterói, Rio de Janeiro, Brazil
S. GARCIA
Affiliation:
Instituto de Biofísica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil Centro de Pesquisas Gonçalo Moniz, Fundação Oswaldo Cruz, Salvador, Bahia, Brazil
L. E. D. GIMÉNEZ
Affiliation:
Instituto de Biofísica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil
C. C. Q. HERNÁNDEZ
Affiliation:
Instituto de Biofísica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil
J. F. V. SENRA
Affiliation:
Centro de Pesquisas Gonçalo Moniz, Fundação Oswaldo Cruz, Salvador, Bahia, Brazil
R. S. LIMA
Affiliation:
Centro de Pesquisas Gonçalo Moniz, Fundação Oswaldo Cruz, Salvador, Bahia, Brazil
F. CYRINO
Affiliation:
Universidade do Estado do Rio de Janeiro, Rio de Janeiro, Brazil
E. BOUSKELA
Affiliation:
Universidade do Estado do Rio de Janeiro, Rio de Janeiro, Brazil
M. B. P. SOARES
Affiliation:
Centro de Pesquisas Gonçalo Moniz, Fundação Oswaldo Cruz, Salvador, Bahia, Brazil
R. RIBEIRO DOS SANTOS
Affiliation:
Centro de Pesquisas Gonçalo Moniz, Fundação Oswaldo Cruz, Salvador, Bahia, Brazil
A. C. CAMPOS DE CARVALHO
Affiliation:
Instituto de Biofísica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil
Get access Rights & Permissions [Opens in a new window]

Abstract

Circulating antibodies in chagasic patients interact with myocardial β adrenergic and muscarinic cholinergic receptors, triggering intracellular signals that alter cardiac function along the course of the disease. However, until now, experimental data in models of chronically infected chagasic mice linking the effects on myocardial β adrenergic and muscarinic receptors to cardiopulmonary dysfunction is lacking. Thus, we studied C57BL/6 mice 8 months after intraperitoneal injection of 100 trypomastigote forms of the Colombian strain of T. cruzi. Uninfected mice, matched in age, were used as controls. Histopathological analyses (inflammation and fibrosis) and radio-ligand binding assays for estimation of muscarinic and adrenergic receptor density were performed in myocardium tissue samples. When compared to controls, infected mice had electrical conduction disturbances, diastolic dysfunction, lower O2 consumption and anaerobic threshold. In addition, hearts of chronic chagasic mice had intense inflammation and fibrosis, and decreased β adrenergic and increased muscarinic receptor densities than normal controls. Our data suggest that chronic T. cruzi infection causes alterations in cardiac receptor density and fibrosis deposition which can be associated with cardiac conduction abnormalities, diastolic dysfunction and lower exercise capacity, associating for the first time all these functional and histopathological alterations in chagasic mice.

Keywords

Chagas' diseasecardiopulmonary functioncardiac receptorsmouse model
Type
Research Article
Information
Parasitology , Volume 133 , Issue 6 , December 2006 , pp. 729 - 737
Copyright
2006 Cambridge University Press

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

References

REFERENCES

Bestetti, R. B. and Oliveira, J. S. ( 1990). The surface electrocardiogram: a simple and reliable method for detecting overt and latent heart disease in rats. Brazilian Journal of Medical and Biological Research 2, 1213–1222.Google Scholar
Borda, E. P., Cossio, P., Vega, M. V., Arana, R. and Sterin-Borda, L. ( 1984). A circulating IgG in Chagas disease which binds to β-adrenoreceptors of myocardium and modulates their activity. Clinical and Experimental Immunology 57, 679–686.Google Scholar
Brener, Z. ( 1973). Biology of Trypanosoma cruzi. Annual Review of Microbiology 27, 347–382.CrossRefGoogle Scholar
Cunha-Neto, E., Duranti, M., Gruber, A., Zingales, B., De Messias I., Stolf, N., Bellotti, G., Patarroyo, M. E., Pilleggi, F. and Kalil, J. ( 1995). Autoimmunity in Chagas disease cardiopathy: biological relevance of a cardiac myosin-specific epitope cross-reactive to an immunodominant Trypanosoma cruzi antigen. Proceedings of the National Academy of Sciences, USA 92, 3541–3545.CrossRefGoogle Scholar
Davila, D. F., Rossell, R. O. and Donis, J. H. ( 1989). Cardiac parasympathetic abnormalities: cause or consequence of Chagas heart disease. Parasitology Today 5, 327–329.CrossRefGoogle Scholar
Dias, J. C. P. ( 1989). The indeterminate form of human chronic Chagas' disease a clinical epidemiological review. Revista da Sociedade Brasileira de Medicina Tropical 22, 147–156.CrossRefGoogle Scholar
Dias, J. C. P. and Coura, J. ( 1997). Clínica e Terapêutica da Doença de Chagas: uma Abordagem Prática Para o Clínico Geral. FIOCRUZ, Rio de Janeiro.CrossRefGoogle Scholar
Engman, D. M. and Leon, J. S. ( 2002). Pathogenesis of Chagas' heart disease: role of autoimmunity. Acta Tropica 81, 123–132.CrossRefGoogle Scholar
Farias, O. S., Pedrosa, R. C., Nascimento, J. H. M., Campos de Carvalho, A. C. and Masuda, M. O. ( 1997). Sera from chronic chagasic patients with complex cardiac arrhythmias depress electrogenesis and conduction in isolated rabbit hearts. Circulation 96, 2031–2037.CrossRefGoogle Scholar
Frederici, E. C., Abelmann, W. N. and Neva, F. A. ( 1964). Chronic and progressive myocarditis in C3H mice infected with Trypanosoma cruzi. American Journal of Tropical Medicine and Hygiene 13, 272–280.CrossRefGoogle Scholar
Garcia, S., Ramos, C. O., Senra, J. F., Vilas-Boas, F., Rodrigues, M. M., Campos-de-Carvalho, A. C., Ribeiro-Dos-Santos, R. and Soares, M. B. ( 2005). Treatment with benznidazole during the chronic phase of experimental Chagas' disease decreases cardiac alterations. Antimicrobial Agents and Chemotherapy 49, 1521–1528.CrossRefGoogle Scholar
Giménez, L. E., Hernández, C. C., Mattos, E. C., Brandão, I. T., Olivieri, B., Campelo, R. P., Araújo-Jorge, T., Silva, C. L., Campos de Carvalho, A. C. and Kurtenbach, E. ( 2005). DNA immunizations with M2 muscarinic and β1 adrenergic receptor coding plasmids impair cardiac function in mice. Journal of Molecular and Cellular Cardiology 38, 703–714.CrossRefGoogle Scholar
Goin, J. C., Borda, E. S., Auger, S., Storino, R. and Sterin-Borda, L. ( 1999). Cardiac M(2) muscarinic cholinoceptor activation by human chagasic autoantibodies: association with bradycardia. Heart 82, 273–278.CrossRefGoogle Scholar
Goin, J. C., Leiros, C. P., Borda, E. and Sterin-Borda, L. ( 1997). Interaction of human chagasic IgG with the second extracellular loop of the human heart muscarinic acetylcholine receptor: functional and pathological implications. FASEB Journal 11, 77–83.CrossRefGoogle Scholar
Gorelik, G., Borda, E., Bacman, S., Cremaschi, G. and Sterin-Borda, L. ( 1992). Chagasic IgG stimulates phosphoinositide hydrolysis via neurotransmitter receptor activation: role of calcium. Journal of Lipid Mediators 5, 249–259.Google Scholar
Hernández, C. C. Q., Barcellos, L. C., Giménez, L. E. D., Cabarcas, R. A. B., Garcia, S., Pedrosa, R. C., Nascimento, J. H. M., Kurtenbach, E., Masuda, M. O. and Carvalho, A. C. C. ( 2003). Human chagasic IgGs bind to cardiac muscarinic receptors and impair L-type Ca2+ currents, Cardiovascular Research 58, 55–65.Google Scholar
Higuchi, M. D., Ries, M. M., Aiello, V. D., Benvenutti, L. D., Gutierrez, P. S., Bellotti, G. and Pileggi, F. ( 1997). Association of an increase in CD8+ T cells with the presence of Trypanosoma cruzi antigens in chronic, human, chagasic myocarditis. American Journal of Tropical Medicine and Hygiene 56, 485–489.CrossRefGoogle Scholar
Köerbele, F. ( 1968). Chagas' disease and Chagas' syndromes: the pathology of American Trypanosomiasis, Advances in Parasitology 6, 63–116.Google Scholar
Masuda, M. O., Levin, M., de Oliveira, S. F., Costa, P. C. S., Bergami, P. L., Almeida, N. A. S., Pedrosa, R. C., Ferrari, I., Hoebeke, J. and Carvalho, A. C. C. ( 1998). Functionally active cardiac antibodies in chronic Chagas disease are specifically blocked by Trypanosoma cruzi antigens. FASEB Journal 12, 1551–1558.CrossRefGoogle Scholar
McCornick, T. S. and Rowland, E. C. ( 1989). Trypanosoma cruzi: croos-reative anti-heart autoantibodies produced during infection in mice. Experimental Parasitology 69, 393–401.CrossRefGoogle Scholar
Mirkin, G. A., Jones, M., Sanz, O. P., Rey, R., Sica, R. E. and Gonzalez Cappa, S. M. ( 1994). Experimental Chagas' disease: electrophysiology and cell composition of the neuromyopathic inflammatory lesions in mice infected with a myotropic and a pantropic strain of Trypanosoma cruzi. Clinical Immunology and Immunopathology 73, 69–79.CrossRefGoogle Scholar
Patrianakos, A. P., Parthenakis, F. L., Papadimitriou, E. A., Diakakis, G. F., Tzerakis, P. G., Nikitovic, D. and Vardas, P. E. ( 2004). Restrictive filling pattern is associated with increased humoral activation and impaired exercise capacity in dilated cardiomyopathy. European Heart Journal 6, 735–743.CrossRefGoogle Scholar
Petkova, S. B., Huang, H., Factor, S. M., Pestell, R. G., Bouzahzah, B., Jelicks, L. A., Weiss, L. M., Douglas, S. A., Wittner, M. and Tanowitz, H. B. ( 2001). The role of endothelin in the pathogenesis of Chagas' disease. International Journal for Parasitology 31, 499–511.CrossRefGoogle Scholar
Rassi, A. and Luquetti, A. Q. ( 1992). Chagas disease (American trypanosomiasis): its impact on transfusion and clinical medicine. In Therapy of Chagas Disease ( ed. Wendel, S., Brener, Z., Camargo, M. G. and Rassi, A.), pp. 237–247. ISBT, Sao Paulo.
Sterin-Borda, L., Gorelik, G. and Borda, E. S ( 1991). Chagasic IgG binding with cardiac muscarinic cholinergic receptors modifies cholinergic-mediated cellular transmembrane signals. Clinical Immunology and Immunopathology 61, 387–397.CrossRefGoogle Scholar
Tanowitz, H. B., Kaul, D. K., Chen, B., Morris, S. A., Factor, S. M., Weiss, L. M. and Wittner, M. ( 1996). Compromised microcirculation in acute murine Trypanosoma cruzi infection. Journal of Parasitology 82, 124–130.CrossRefGoogle Scholar
Tarleton, R. L. ( 2001). Parasite persistence in the aetiology of Chagas disease. International Journal for Parasitology 31, 550–554.CrossRefGoogle Scholar
Wang, L., Wirp, S. and Duff, H. ( 2000). Age-dependent response of the electrocardiogram to K(+) channel blockers in mice. American Journal of Physiology 278, C73–C78.CrossRefGoogle Scholar
WORLD HEALTH ORGANIZATION ( 1995). Chagas' disease: important advances in elimination of transmission in four countries in Latin America. WHO Press Office Feature, Geneva, Switzerland.