ABSTRACT
Endothelin alters central sympathetic responses, but the resultant effects on arrhythmogenesis are unknown. We examined ventricular tachyarrhythmias after endothelin receptor-A blockade in the brain of Wistar rats with acute myocardial infarction. For this aim, BQ-123 (n=6) or phosphate-buffered saline (n=6) were injected intracerebroventricularly. After 10 min, the left coronary artery was ligated, followed by implantation of telemetry transmitters. Electrocardiography and voluntary activity (as a surrogate of acute left ventricular failure) were continuously monitored for 24 h. Infarct-size was similar in the two groups. There were fewer episodes of ventricular tachyarrhythmias of shorter average duration in treated rats, leading to markedly shorter total duration (12.3+/-8.9 s), when compared to controls (546.2+/-130.3 s). Voluntary activity increased in treated rats during the last hours of recording, but bradyarrhythmic episodes were comparable between the two groups. Endothelin receptor-A blockade in the brain of rats decreases the incidence of ventricular tachyarrhythmias post-ligation, without affecting bradyarrhythmic episodes. These findings call for further research on the pathophysiologic role of endothelin during acute myocardial infarction.
Subject(s)
Cerebral Ventricles/drug effects , Endothelin A Receptor Antagonists/administration & dosage , Myocardial Infarction/drug therapy , Peptides, Cyclic/administration & dosage , Receptor, Endothelin A/drug effects , Tachycardia, Ventricular/prevention & control , Ventricular Premature Complexes/prevention & control , Animals , Cerebral Ventricles/metabolism , Cerebral Ventricles/physiopathology , Disease Models, Animal , Injections, Intraventricular , Myocardial Infarction/complications , Myocardial Infarction/metabolism , Myocardial Infarction/physiopathology , Rats, Wistar , Receptor, Endothelin A/metabolism , Tachycardia, Ventricular/etiology , Tachycardia, Ventricular/metabolism , Tachycardia, Ventricular/physiopathology , Ventricular Premature Complexes/etiology , Ventricular Premature Complexes/metabolism , Ventricular Premature Complexes/physiopathologyABSTRACT
AIM: To investigate the effect of carvacrol on chemical carcinogenesis, cancer cell proliferation and platelet aggregation, and to find possible correlation between all these processes and the antioxidant properties of carvacrol. MATERIALS AND METHODS: 3,4-benzopyrene-induced carcinogenesis model using Wistar rats was used. Leiomyosarcoma cells from Wistar rats were used to study carvacrol antiproliferative activity in vitro. The carvacrol antiplatelet properties were investigated with platelet aggregation assay and flow cytometry technique. The production of thromboxane B2, final metabolite of platelet aggregation, was evaluated by radioimmunoassay. RESULTS: Our study revealed significant anticarcinogenic properties of carvacrol. We observed 30% decrease of 3,4 benzopyrene carcinogenic activity in vivo. Antiproliferative activity of carvacrol (IC(50)) was 90 microM and 67 microM for 24 h and 48 h of incubation of cells, respectively. Carvacrol possessed also mild antiplatelet effect, inducing the decrease of thromboxane A2 production in platelets and as a result - restrictive expression of the GPIIb/IIIa platelet receptor. CONCLUSION: Our data demonstrated that carvacrol possesses anticarcinogenic, antiproliferative and antiplatelet properties.
