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Abstract Aim: This study was designed to investigate the effects of ivabradine versus metoprolol on cardiovascular changes and the infarction size induced by isoprenaline in chronic N-nitro-L-arginine methyl ester (L-NAME) treated rats and digoxin induced ventricular dysrhythmia. Methods: Experiment one, four groups of male Wistar rats were studied: control group, L-NAME treated group (100mg/kg), L-NAME (100mg/kg) and ivabradine (10mg/kg) treated group and L-NAME (100mg/kg) and metoprolol (150mg/kg) treated group. All treatments were administered daily by gavage. After 6 weeks of L-NAME treatment myocardial infarction was induced by isoprenaline injection (11mg/100g/day i.p. for 2 consecutive days). Experiment two, three groups of rats were studied: digoxin, ivabradine and metoprolol groups. Systolic blood pressure and electrocardiograph were monitored. Cardiac marker enzymes were measured and histopathological examination of heart tissues, aorta and coronary vessels were performed. Vascular reactivity of the isolated aortic ring was done. Results: Ivabradine and metoprolol administration to L-NAME/ isoprenaline treated rats significantly reduced heart rate, microvascular remodeling, the infarct size, serum lactate dehydrogenase and creatine kinase and attenuated the mortality resulting from isoprenaline induced infarction. Treatment with ivabradine had non-significant effect against L-NAME induced hypertension and cardiac hypertrophy, while metoprolol had a significant effect. Ivabradine improves endothelial function, and reduces atherosclerotic plaque formation in L-NAME treated rats. On the contrary, metoprolol reduced atherosclerosis in L-NAME treated rats with no effect on endothelial function. Ivabradine could not protect against digoxin induced ventricular dysrhythmia while metoprolol showed protective effect. Conclusion: These results suggest that ivabradine has a significant protective effect against isoprenaline-induced myocardial infarction, endothelial dysfunction and atherosclerosis in chronic L-NAME-treated rat. Key words: Ivabradine; metoprolol; NG-nitro-L-arginine methyl ester (L-NAME); atherosclerosis. |