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Original Article
Egyptian Journal of Basic and Clinical Pharmacology
Vol. 2 (2012), Issue 1, pp. 26-40
doi:10.11131/2012/101333

Differential Effects of Ivabradine and Metoprolol on Cardiovascular Remodeling and Myocardial Infarction Induced by Isoprenaline in Chronic N-nitro-L-arginine Methyl Ester (L-NAME) Treated Rats

Nevein Hendawy1, Amany Helmy1, Hala Salah Abdel Kawy1, Ghada Karouk Mohamed2, Ahmed El Sayed Badawy1, and Hoda Sallam1

1Department of Pharmacology, Faculty of Medicine, Ain Shams University. Cairo, Egypt

2Department of Histology, Faculty of Medicine, Ain Shams University. Cairo, Egypt


Copyright © 2012 Nevein Hendawy et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Background: Elevated heart rate is associated with cardiovascular morbidity and mortality in the general population and in patients with cardiovascular disease Aim: This study was designed to investigate the effects of the two bradycardiac agents ivabradine and metoprolol on cardiovascular changes and the infarction size induced by isoprenaline in chronic N-nitro-L-arginine methyl ester (L-NAME) treated rats. Methods: Four groups of male Wistar rats were studied: the 1st group served as a normal control, the 2nd received L-NAME (100 mg/kg), the 3rd group was treated with the same dose of L-NAME plus ivabradine (10 mg/kg) and the 4th group was treated with the same dose of L-NAME plus metoprolol (150 mg/kg). All treatments were administered daily by gastric gavage. After 6 weeks of L-NAME and drug treatment myocardial infarction was induced by isoprenaline injection (11 mg/100g/day for 2 consecutive days). The following parameters were assessed; systolic blood pressure, electrocardiographic changes, cardiac enzymes, and histopathological examination of heart tissues, aorta & coronary vessels. Moreover, vascular reactivity of the isolated aortic rings to phenylephrine and acetylcholine was tested. Results: Ivabradine and metoprolol administration to L-NAME/isoprenaline treated rats significantly reduced heart rate, microvascular remodeling, infarct size, serum lactate dehydrogenase, serum creatine kinase and attenuated the mortality resulting from isoprenaline-induced infarction. Pretreatment with ivabradine had non-significant effect on L-NAME-induced hypertension and cardiac hypertrophy, in contrast to metoprolol pretreatment. Selective heart rate reduction with ivabradine improved endothelial dysfunction, and reduced atherosclerotic plaque formation in L-NAME treated rats. On the contrary, metoprolol showed insignificant improvement of endothelial dysfunction as evidenced by assessment of mean EC50 and Emax of phenylephrine-induced contraction and by considering the mean percent of acetylcholine-induced relaxation in comparison to the L-NAME/isoprenaline treated group. Conclusion, these results suggest that ivabradine has a significant protective effect against isoprenaline-induced myocardial infarction with improvement of endothelial dysfunction in chronic L-NAME-treated rats.

Original Article
Egyptian Journal of Basic and Clinical Pharmacology
Vol. 2 (2012), Issue 1, pp. 26-40
doi:10.11131/2012/101333

Differential Effects of Ivabradine and Metoprolol on Cardiovascular Remodeling and Myocardial Infarction Induced by Isoprenaline in Chronic N-nitro-L-arginine Methyl Ester (L-NAME) Treated Rats

Nevein Hendawy1, Amany Helmy1, Hala Salah Abdel Kawy1, Ghada Karouk Mohamed2, Ahmed El Sayed Badawy1, and Hoda Sallam1

1Department of Pharmacology, Faculty of Medicine, Ain Shams University. Cairo, Egypt

2Department of Histology, Faculty of Medicine, Ain Shams University. Cairo, Egypt


Copyright © 2012 Nevein Hendawy et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Background: Elevated heart rate is associated with cardiovascular morbidity and mortality in the general population and in patients with cardiovascular disease Aim: This study was designed to investigate the effects of the two bradycardiac agents ivabradine and metoprolol on cardiovascular changes and the infarction size induced by isoprenaline in chronic N-nitro-L-arginine methyl ester (L-NAME) treated rats. Methods: Four groups of male Wistar rats were studied: the 1st group served as a normal control, the 2nd received L-NAME (100 mg/kg), the 3rd group was treated with the same dose of L-NAME plus ivabradine (10 mg/kg) and the 4th group was treated with the same dose of L-NAME plus metoprolol (150 mg/kg). All treatments were administered daily by gastric gavage. After 6 weeks of L-NAME and drug treatment myocardial infarction was induced by isoprenaline injection (11 mg/100g/day for 2 consecutive days). The following parameters were assessed; systolic blood pressure, electrocardiographic changes, cardiac enzymes, and histopathological examination of heart tissues, aorta & coronary vessels. Moreover, vascular reactivity of the isolated aortic rings to phenylephrine and acetylcholine was tested. Results: Ivabradine and metoprolol administration to L-NAME/isoprenaline treated rats significantly reduced heart rate, microvascular remodeling, infarct size, serum lactate dehydrogenase, serum creatine kinase and attenuated the mortality resulting from isoprenaline-induced infarction. Pretreatment with ivabradine had non-significant effect on L-NAME-induced hypertension and cardiac hypertrophy, in contrast to metoprolol pretreatment. Selective heart rate reduction with ivabradine improved endothelial dysfunction, and reduced atherosclerotic plaque formation in L-NAME treated rats. On the contrary, metoprolol showed insignificant improvement of endothelial dysfunction as evidenced by assessment of mean EC50 and Emax of phenylephrine-induced contraction and by considering the mean percent of acetylcholine-induced relaxation in comparison to the L-NAME/isoprenaline treated group. Conclusion, these results suggest that ivabradine has a significant protective effect against isoprenaline-induced myocardial infarction with improvement of endothelial dysfunction in chronic L-NAME-treated rats.

Original Article
Egyptian Journal of Basic and Clinical Pharmacology
Vol. 2 (2012), Issue 1, pp. 26-40
doi:10.11131/2012/101333

Differential Effects of Ivabradine and Metoprolol on Cardiovascular Remodeling and Myocardial Infarction Induced by Isoprenaline in Chronic N-nitro-L-arginine Methyl Ester (L-NAME) Treated Rats

Nevein Hendawy1, Amany Helmy1, Hala Salah Abdel Kawy1, Ghada Karouk Mohamed2, Ahmed El Sayed Badawy1, and Hoda Sallam1

1Department of Pharmacology, Faculty of Medicine, Ain Shams University. Cairo, Egypt

2Department of Histology, Faculty of Medicine, Ain Shams University. Cairo, Egypt


Copyright © 2012 Nevein Hendawy et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

How to Cite this Article

Nevein Hendawy, Amany Helmy, Hala Salah Abdel Kawy, Ghada Karouk Mohamed, Ahmed El Sayed Badawy, and Hoda Sallam, “Differential Effects of Ivabradine and Metoprolol on Cardiovascular Remodeling and Myocardial Infarction Induced by Isoprenaline in Chronic N-nitro-L-arginine Methyl Ester (L-NAME) Treated Rats,” Egyptian Journal of Basic and Clinical Pharmacology, Vol. 2, Issue 1, pp. 26-40, 2012. doi:10.11131/2012/101333