Electrophysiological and pharmacological evaluation of the nicotinic cholinergic system in chagasic rats

BMC Clinical Pharmacology

Claudina Rodríguez-Bonfante¹  Marcos Durand Mena²  Lady Ferrer Mancini¹  Ruth Fonseca Zambrano¹  Eliezer Jiménez Hernández¹  Erlymar López Hincapié¹  Rafael Bonfante-Cabarcas¹ 

[1]Libertador Av. con Andrés Bello, Unidad de Bioquímica, Decanato de Ciencias de la Salud, Universidad Centro-Occidental “Lisandro Alvarado”, Barquisimeto, Estado Lara, Código Postal: 3001, Venezuela

[2]Biochemistry Research Units, Health Sciences School, Universidad Centro Occidental Lisandro Alvarado, Barquisimeto, Lara, Venezuela

关键词: α-BGT;    DHβE;    Mecamylamine;    Chagas disease;    Nicotine;    Isolated beating hearts;    Vagal stimulation;   

Others  :  860688
DOI  :  10.1186/2050-6511-14-2

 received in 2012-04-11, accepted in 2012-12-21,  发布年份 2013

【 摘 要 】

Background

Two theories attempt to explain the changes observed in the nicotinic acetylcholine receptors (nAChRs) in chagasic cardiomyopathy. The neurogenic theory proposes that receptor changes are due to loss of intracardiac ganglia parasympathetic neurons. The immunogenic theory proposes that the nAChRs changes are the result of autoantibodies against these receptors. Both theories agreed that nAChRs functional expression could be impaired in Chagas disease.

Methods

We evaluated nAChRs functional integrity in 54 Sprague Dawley rats, divided in two groups: healthy and chronic chagasic rats. Rats were subjected to electrocardiographic studies in the whole animal under pentobarbital anesthesia, by isolation and stimulation of vagus nerves and in isolated beating hearts (Langendorff’s preparation).

Results

Nicotine, 10 μM, induced a significant bradycardia in both groups. However, rats that had previously received reserpine did not respond to nicotine stimulation. β-adrenergic stimulation, followed by nicotine treatment, induced tachycardia in chagasic rats; while inducing bradycardia in healthy rats. Bilateral vagus nerve stimulation induced a significantly higher level of bradycardia in healthy rats, compared to chagasic rats; physostigmine potentiated the bradycardic response to vagal stimulation in both experimental groups. Electric stimulation (e.g., ≥ 2 Hz), in the presence of physostigmine, produced a comparable vagal response in both groups. In isolated beating-heart preparations 1 μM nicotine induced sustained bradycardia in healthy hearts while inducing tachycardia in chagasic hearts. Higher nicotine doses (e.g.,10 – 100 uM) promoted the characteristic biphasic response (i.e., bradycardia followed by tachycardia) in both groups. 10 nM DHβE antagonized the effect of 10 μM nicotine, unmasking the cholinergic bradycardic effect in healthy rats only. 1 nM α-BGT alone induced bradycardia in healthy hearts but antagonized the 10 μM nicotine-induced tachycardia in chagasic rats. In healthy but not in chagasic hearts, 10 μM nicotine shortened PQ and PR interval, an effect counteracted by MA, DHβE and αBGT

Conclusion

Our results suggest that cholinergic function is impaired in chronic Chagas disease in rats, a phenomena that could be related to alteration on the nAChR expression.

【 授权许可】

   
2013 Bonfante-Cabarcas et al.; licensee BioMed Central Ltd.

【 图 表 】

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