The cholinergic system in cyclophosphamide-induced Chagas dilated myocardiopathy in Trypanosoma-cruzi-infected rats: an electrocardiographic study.
Chronic Chagasic Cardiomyopathy (CCC) has been related to the cholinergic system by the neurogenic and autoimmune theories. The neurogenic theory explains cardiomyopathy as a result of post-ganglionic parasympathetic denervation. Cyclophosphamide (CP) facilitates the development of autoimmune disease because of a selective depletion of suppressor T cells. In this study we characterized the phenylephrine-induced vasovagal reflex using selective cholinergic drugs, in two rat models: Trypanosoma cruzi (TC) infected animals and CCC CP-treated rat model. To achieve this goal, 3 week old-90 Sprague Dawley rats were divided into four groups: Control (C), CP, TC and TCCP; TC and TCCP were inoculated with 1000 trypomastigotes/g; CP and TCCP were treated with CP 20 mg/Kg twice a week for five times. After 6 months, the studied animals underwent electrocardiographic (EKG), radiographic (Rx) and histopathological (HP) assesments. The vagal integrity was evaluated by application of phenylephrine (PE) plus tacrine, while the muscarinic cholinergic function was evaluated using selective M1, M2, M3 and M4 muscarinic antagonists. Our data show show that TCCP rats displayed the highest frequency of EKG, Rx and HP disturbances. TC and TCCP rats exhibited a decreased response to: 1) phenylephrine-induced vagal baroreflex bradycardia; 2) methoctramine-, 4-DAMP- and tropicamide-induced tachycardia; 3) methoctramine-induced QRS shortening, and 4) tropicamide-induced QT prolongation. In conclusion, CP facilitates the development of CCC in Trypanosoma cruzi infected rats, by promoting parasympathetic disturbances that appear as consequence of alterations on the muscarinic receptor distribution at different neural integration levels.
Labrador-Hernández
Marialeycnan
M
Unidad de Bioquímica José Antonio Moreno Yanes, Decanato de Medicina, Universidad Centro-Occidental Lisandro Alvarado, Barquisimeto, Venezuela.
Suárez-Graterol
Oscar
O
Romero-Contreras
Urimare
U
Rumenoff
Lila
L
Rodríguez-Bonfante
Claudina
C
Bonfante-Cabarcas
Rafael
R
D000109:Acetylcholine / Q000502:physiology*; D000818:Animals; D020274:Autoimmune Diseases of the Nervous System / Q000139:chemically induced / Q000209:etiology / Q000503:physiopathology; D017704:Baroreflex / Q000187:drug effects / Q000502:physiology; D001919:Bradycardia / Q000139:chemically induced / Q000503:physiopathology; D018414:CD8-Positive T-Lymphocytes / Q000187:drug effects / Q000276:immunology; D002598:Chagas Cardiomyopathy / Q000139:chemically induced / Q000000981:diagnostic imaging / Q000276:immunology / Q000473:pathology / Q000503:physiopathology*; D003520:Cyclophosphamide / Q000633:toxicity*; D003959:Diamines / Q000494:pharmacology; D004562:Electrocardiography; D008954:Models, Biological; D018727:Muscarinic Antagonists / Q000494:pharmacology; D010656:Phenylephrine / Q000494:pharmacology; D011859:Radiography; D051381:Rats; D017207:Rats, Sprague-Dawley; D011976:Receptors, Muscarinic / Q000502:physiology*; D012021:Reflex, Abnormal; D013619:Tacrine / Q000494:pharmacology; D014331:Tropicamide / Q000494:pharmacology; D014630:Vagus Nerve / Q000187:drug effects / Q000503:physiopathology*; D014661:Vasoconstriction / Q000187:drug effects / Q000502:physiology
D003959:Diamines; D018727:Muscarinic Antagonists; D011976:Receptors, Muscarinic; D010656:Phenylephrine; D013619:Tacrine; D003520:Cyclophosphamide; D014331:Tropicamide; D000109:Acetylcholine; C054938:methoctramine