TITLE:
A Decreased Expression and Functionality of Muscarinic Cholinergic Receptor in Acute Chagas Myocarditis
AUTHORS:
M. Labrador-Hernández, L. Jiménez, G. Leon, R. López, W. Mendoza, C. Bonfante-Rodriguez, J. Torres-Peraza, R. Bonfante-Cabarcas
KEYWORDS:
Acute Chagas Disease, Muscarinic Receptors, Oxotremorine, CsCl, McN-A-343, Phenyleprhine, Pirenzepine, [3H]-QNB, Sprague Dawley Rats
JOURNAL NAME:
World Journal of Cardiovascular Diseases,
Vol.4 No.6,
May
30,
2014
ABSTRACT: Background: Chagas disease is still a public health problem because of the remaining high prevalence, the expansion of the disease into developed countries and the re-emergences by oral transmission outbreaks. Chagas cardiomyopathy evolves as a consequence of an autonomic un-balance where the parasympathetic tone is undermined. Objective: To determine the functionality and expression of muscarinic cholinergic receptors in acute Chagas disease. Methodology: 62 male, 3-week-old Sprague Dawley rats were assayed; 32 were infected with Trypanosoma cruzi trypo-mastigotes and 30 were healthy controls. Electrocardiographic studies were conducted in the absence or presence of direct muscarinic (oxotremorine and McN-A-343) or indirect agonists (phenylephrine) or antagonist (pirenzepine). Muscarinic M1 and M2 receptor expression was determined by radioligand [3H]-QNB binding assay and immunoblot. Results: Chagasic acute myocarditis was sustained by electrocardiographic signs and histopathological findings. Bradycardia induced by oxotremorine was significantly higher in healthy rats (HR) and the differences were enhanced by CsCl. In the absence of the agonist, CsCl induced a greater bradycardia in chagasic rats (ChR). In HR McN-A-343 induced tachycardia, however it induces bradycardia in the presence of a acetylcholinesterase inhibitor (neostigmine); no effects were observed in ChR. Pirenzepine induced a higher tachycardia in HR. Phenylephrine in the presence of pirenzepine induced a similar bradycardia in both groups, but recovery was faster in ChR. Muscarinic M1 and M2 receptor density was higher in HR. Conclusion: Muscarinic receptor expression and functionality are decreased in the acute Chagas disease that could impact the evolution and prognosis of the disease.