Advertisement

Cardiovascular Toxicology

, Volume 12, Issue 2, pp 166–174 | Cite as

Comparing Effects of Lacidipine, Ramipril, and Valsartan Against Experimentally Induced Myocardial Infarcted Rats

  • Yasin BayirEmail author
  • Zekai Halici
  • Emre Karakus
  • Abdulmecit Albayrak
  • Irmak Ferah
  • Esref Kabalar
  • Osman Keles
  • Mevlut Sait Keles
  • Bunyami Unal
Article

Abstract

In this study, the effects of lacidipine (LAC), ramipril (RAM), and valsartan (VAL) on biochemical and histopathologic changes in heart tissue were studied in rats with isoproterenol-induced (ISO-induced) myocardial infarction (MI). LAC, RAM, and VAL had been administered via oral gavage at 3, 3, and 30 mg/kg doses, respectively, once per day during a 30-day time period. On days 29 and 30, the drug treatment group and the control group (with the exception of the intact control group, in which no medications were given, and ISO was not administered) were administered 180 mg/kg ISO subcutaneously over an interval of 24 h. After this period, the hearts of the rats were removed and processed for biochemical and histopathologic studies. The antioxidant parameters superoxide dismutase (SOD), catalase (CAT), and malondialdehyde (MDA) were estimated. A diagnosis of MI was confirmed with antioxidant parameters and histopathologic findings. In MI control groups, histopathologic indicators were found to be statistically higher than those in drug groups; an increase in histopathologic indicators of MI correlates with significant decreases in SOD and CAT levels, and an increase in MDA level. Histopathologic grades of MI indicators were significantly higher in MI group that did not receive any cardioprotective medications in comparison with MI groups that received LAC, RAM, and VAL. Each of the three medications favorably modulated most of the biochemical and histopathologic parameters observed. No significant difference existed with regard to any of the estimated parameters in the rat groups that received medications without MI induction. In conclusion, results indicate that LAC, RAM, and VAL significantly reduced myocardial injury and emphasize the cardioprotective nature of these agents.

Keywords

Isoproterenol Rat Myocardial infarction Ramipril Lacidipine Valsartan 

Notes

Acknowledgments

The author (Y. Bayir) wishes to thank Associated Professors Fehmi Odabasoglu, Yalcin Karagoz, Elif Cadirci, Mesut Halici; and the Bachelor of Sciences students, Fadime Atalay and Selma Mutlu, for their kind support during this doctorate study.

References

  1. 1.
    Gupta, S., Mohanty, I. & Talwar, K. (2004). Cardioprotection from ischemia and reperfusion injury by Withania somnifera: A hemodynamic, biochemical and histopathological assessment. Molecular Cell Biochemistry, 260, 39–47.CrossRefGoogle Scholar
  2. 2.
    Hertog, M. G. L., Feskens, E. J. M., Hollman, P. C. H., Katan, M. B., & Kromhout, D. (1993). Dietary antioxidant flavonoids and risk of coronary heart-disease—The Zutphen Elderly Study. Lancet, 342, 1007–1011.PubMedCrossRefGoogle Scholar
  3. 3.
    Sumitra, M., Manikandan, P., Kumar, D. A., Arutselvan, N., Manohar, B. M., & Puvanakrishnan, R. (2001). Experimental myocardial necrosis in rats: role of arjunolic acid on platelet aggregation, coagulation and antioxidant status. Molecular and Cellular Biochemistry, 224, 135–142.PubMedCrossRefGoogle Scholar
  4. 4.
    Vaage, J., & Valen, G. (1993). Pathophysiology and mediators of ischemia-reperfusion injury with special reference to cardiac surgery. A review. Scandinavian Journal of Thoracic and Cardiovascular Surgery. Supplementum, 41, 1–18.PubMedCrossRefGoogle Scholar
  5. 5.
    Rajadurai, M., & Prince, P. S. (2007). Preventive effect of naringin on isoproterenol-induced cardiotoxicity in Wistar rats: An in vivo and in vitro study. Toxicology, 232, 216–225.PubMedCrossRefGoogle Scholar
  6. 6.
    Wexler, B. C., & Greenberg, B. P. (1978). Protective effects of clofibrate on isoproterenol-induced myocardial-infarction in arteriosclerotic and non-arteriosclerotic rats. Atherosclerosis, 29, 373–395.PubMedCrossRefGoogle Scholar
  7. 7.
    Cao, A. P., Loyzaga, P. G., Peter, A. M., & Iamargo, J. (1994). Effect of oxidipine and pitredipine on the size of experimental myocardial infarction in the rats. Pharmacology and Toxicology, 74, 321–329.CrossRefGoogle Scholar
  8. 8.
    Nair, P. S., & Shyamala Devi, C. S. (2006). Efficacy of mangiferin on serum and heart tissue lipids in rats subjected to isoproterenol induced cardiotoxicity. Toxicology, 228, 135–139.PubMedCrossRefGoogle Scholar
  9. 9.
    Keles, M. S., Bayir, Y., Suleyman, H., & Halici, Z. (2009). Investigation of effects of Lacidipine, Ramipril and Valsartan on DNA damage and oxidative stress occurred in acute and chronic periods following isoproterenol-induced myocardial infarct in rats. Molecular and Cellular Biochemistry, 328, 109–117.PubMedCrossRefGoogle Scholar
  10. 10.
    Nirmala, C., & Puvanakrishnan, R. (1994). Isoproterenol-induced myocardial-infarction in rats—Functional and biochemical-alterations. Medical Science Research, 22, 575–577.Google Scholar
  11. 11.
    Singh, D., & Chopra, K. (2004). The effect of naringin, a bioflavonoid on ischemia-reperfusion induced renal injury in rats. Pharmacological Research, 50, 187–193.PubMedCrossRefGoogle Scholar
  12. 12.
    Sharma, M., Kishore, K., Gupta, S. K., Joshi, S., & Arya, D. S. (2001). Cardioprotective potential of ocimum sanctum in isoproterenol induced myocardial infarction in rats. Molecular and Cellular Biochemistry, 225, 75–83.PubMedCrossRefGoogle Scholar
  13. 13.
    Kyselovic, J., Krenek, P., Wibo, M., & Godfraind, T. (2001). Effects of amlodipine and lacidipine on cardiac remodelling and renin production in salt-loaded stroke-prone hypertensive rats. British Journal of Pharmacology, 134, 1516–1522.PubMedCrossRefGoogle Scholar
  14. 14.
    Wolkart, G., Pang, X., Stessel, H., Kirchengast, M., & Brunner, F. (2007). Chronic endothelin-A receptor antagonism is as protective as angiotensin converting enzyme inhibition against cardiac dysfunction in diabetic rats. British Journal of Pharmacology, 151, 1187–1197.PubMedCrossRefGoogle Scholar
  15. 15.
    Yu, C. M., Wing-Hon Lai, K., Li, P. S., Lam, K. Y., Leung, J. C., & Lai, K. N. (2004). Normalization of renal aquaporin-2 water channel expression by fosinopril, valsartan, and combination therapy in congestive heart failure: a new mechanism of action. Journal of Molecular and Cellular Cardiology, 36, 445–453.PubMedCrossRefGoogle Scholar
  16. 16.
    Rona, G., Chappel, C. I., Balazs, T., & Gaudry, R. (1959). An infarct-like myocardial lesion and other toxic manifestations produced by isoproterenol in the rat. AMA Arch Pathol, 67, 443–455.PubMedGoogle Scholar
  17. 17.
    Sun, Y., Oberley, L. W., & Li, Y. (1988). A simple method for clinical assay of superoxide dismutase. Clinical Chemistry, 34, 497–500.PubMedGoogle Scholar
  18. 18.
    Aebi, H. (1984). Catalase in vitro. Methods in Enzymology, 105, 121–126.PubMedCrossRefGoogle Scholar
  19. 19.
    Ohkawa, H., Ohishi, N., & Yagi, K. (1979). Assay for lipid peroxides in animal tissues by thiobarbituric acid reaction. Analytical Biochemistry, 95, 351–358.PubMedCrossRefGoogle Scholar
  20. 20.
    Bayir, Y., Odabasoglu, F., Cakir, A., Aslan, A., Suleyman, H., Halici, M., et al. (2006). The inhibition of gastric mucosal lesion, oxidative stress and neutrophil-infiltration in rats by the lichen constituent diffractaic acid. Phytomedicine, 13, 584–590.PubMedCrossRefGoogle Scholar
  21. 21.
    Gundersen, H. J. (1988). The nucleator. Journal of Microscopy, 151, 3–21.PubMedCrossRefGoogle Scholar
  22. 22.
    Mattfeldt, T., Mall, G., Gharehbaghi, H., & Moller, P. (1990). Estimation of surface area and length with the orientator. Journal of Microscopy, 159, 301–317.PubMedCrossRefGoogle Scholar
  23. 23.
    Nyengaard, J. R., & Gundersen, H. J. G. (1992). The Isector—A simple and direct method for generating isotropic, uniform random sections from small specimens. Journal of Microscopy-Oxford, 165, 427–431.CrossRefGoogle Scholar
  24. 24.
    Dorph-Petersen, K. A., Pierri, J. N., Sun, Z., Sampson, A. R., & Lewis, D. A. (2004). Stereological analysis of the mediodorsal thalamic nucleus in schizophrenia: Volume, neuron number, and cell types. The Journal of Comparative Neurology, 472, 449–462.PubMedCrossRefGoogle Scholar
  25. 25.
    Rona, G. (1985). Catecholamine cardiotoxicity. Journal of Molecular and Cellular Cardiology, 17, 291–306.PubMedCrossRefGoogle Scholar
  26. 26.
    Kumari, S. S., & Menon, V. P. (1987). Changes in levels of lipid peroxides and activities of superoxide dismutase and catalase in isoproterenol induced myocardial infarction in rats. Indian Journal of Experimental Biology, 25, 419–423.PubMedGoogle Scholar
  27. 27.
    Hirsch, A. T., Talsness, C. E., Schunkert, H., Paul, M., & Dzau, V. J. (1991). Tissue-specific activation of cardiac angiotensin converting enzyme in experimental heart failure. Circulation Research, 69, 475–482.PubMedGoogle Scholar
  28. 28.
    Zhu, Y. Z., Zhu, Y. C., Li, J., Schafer, H., Schmidt, W., Yao, T., et al. (2000). Effects of losartan on haemodynamic parameters and angiotensin receptor mRNA levels in rat heart after myocardial infarction. Journal of the Renin-Angiotensin-Aldosterone System : JRAAS, 1, 257–262.PubMedCrossRefGoogle Scholar
  29. 29.
    Lindpaintner, K., Lu, W., Neidermajer, N., Schieffer, B., Just, H., Ganten, D., et al. (1993). Selective activation of cardiac angiotensinogen gene expression in post-infarction ventricular remodeling in the rat. Journal of Molecular and Cellular Cardiology, 25, 133–143.PubMedCrossRefGoogle Scholar
  30. 30.
    Meggs, L. G., Coupet, J., Huang, H., Cheng, W., Li, P., Capasso, J. M., et al. (1993). Regulation of angiotensin II receptors on ventricular myocytes after myocardial infarction in rats. Circulation Research, 72, 1149–1162.PubMedGoogle Scholar
  31. 31.
    Nio, Y., Matsubara, H., Murasawa, S., Kanasaki, M., & Inada, M. (1995). Regulation of gene transcription of angiotensin II receptor subtypes in myocardial infarction. The Journal of Clinical Investigation, 95, 46–54.PubMedCrossRefGoogle Scholar
  32. 32.
    Sladek, T., Sladkova, J., Kolar, F., Papousek, F., Cicutti, N., Korecky, B., et al. (1996). The effect of AT1 receptor antagonist on chronic cardiac response to coronary artery ligation in rats. Cardiovascular Research, 31, 568–576.PubMedGoogle Scholar
  33. 33.
    Pfeffer, M. A., Braunwald, E., Moye, L. A., Basta, L., Brown, E. J., Jr, Cuddy, T. E., et al. (1992). Effect of captopril on mortality and morbidity in patients with left ventricular dysfunction after myocardial infarction. Results of the survival and ventricular enlargement trial. The SAVE Investigators. The New England Journal of Medicine, 327, 669–677.PubMedCrossRefGoogle Scholar
  34. 34.
    Thompson, J. A., & Hess, M. L. (1986). The oxygen free radical system: a fundamental mechanism in the production of myocardial necrosis. Progress in Cardiovascular Diseases, 28, 449–462.PubMedCrossRefGoogle Scholar
  35. 35.
    Cohen, M. V. (1978). The functional value of coronary collaterals in myocardial ischemia and therapeutic approach to enhance collateral flow. American Heart Journal, 95, 396–404.PubMedCrossRefGoogle Scholar
  36. 36.
    Bolli, R. (1990). Mechanism of myocardial “stunning”. Circulation, 82, 723–738.PubMedCrossRefGoogle Scholar
  37. 37.
    Nath, K. A., & Norby, S. M. (2000). Reactive oxygen species and acute renal failure. American Journal of Medicine, 109, 665–678.PubMedCrossRefGoogle Scholar
  38. 38.
    Karthikeyan, K., Bai, B. R., & Devaraj, S. N. (2007). Cardioprotective effect of grape seed proanthocyanidins on isoproterenol-induced myocardial injury in rats. International Journal of Cardiology, 115, 326–333.PubMedCrossRefGoogle Scholar
  39. 39.
    Padmanabhan, M., & Prince, P. S. (2006). Preventive effect of S-allylcysteine on lipid peroxides and antioxidants in normal and isoproterenol-induced cardiotoxicity in rats: a histopathological study. Toxicology, 224, 128–137.PubMedCrossRefGoogle Scholar
  40. 40.
    Mohanty, I., Arya, D. S., Dinda, A., Talwar, K. K., Joshi, S., & Gupta, S. K. (2004). Mechanisms of cardioprotective effect of Withania somnifera in experimentally induced myocardial infarction. Basic & Clinical Pharmacology & Toxicol, 94, 184–190.Google Scholar
  41. 41.
    Mladenka, P., Zatloukalova, L., Simunek, T., Bobrovova, Z., Semecky, V., Nachtigal, P., et al. (2009). Direct administration of rutin does not protect against catecholamine cardiotoxicity. Toxicology, 255, 25–32.PubMedCrossRefGoogle Scholar
  42. 42.
    Albayrak, F., Bayir, Y., Halici, Z., Kabalar, E., Bayram, E., Ozturk, C., et al. (2009). Preventive effect of amiodarone during acute period in isoproterenol-induced myocardial injury in Wistar rats. Cardiovascular Toxicology, 9, 161–168.PubMedCrossRefGoogle Scholar
  43. 43.
    Sandmann, S., Claas, R., Cleutjens, J. P., Daemen, M. J., & Unger, T. (2001). Calcium channel blockade limits cardiac remodeling and improves cardiac function in myocardial infarction-induced heart failure in rats. Journal of Cardiovascular Pharmacology, 37, 64–77.PubMedCrossRefGoogle Scholar
  44. 44.
    Tisne-Versailles, J., Constantin, M., Lamar, J. C., & Pourrias, B. (1985). Cardiotoxicity of high doses of isoproterenol on cardiac haemodynamics and metabolism in SHR and WKY rats. Archives Internationales de Pharmacodynamie et de Therapie, 273, 142–154.PubMedGoogle Scholar
  45. 45.
    Grimm, D., Elsner, D., Schunkert, H., Pfeifer, M., Griese, D., Bruckschlegel, G., et al. (1998). Development of heart failure following isoproterenol administration in the rat: role of the renin-angiotensin system. Cardiovascular Research, 37, 91–100.PubMedCrossRefGoogle Scholar
  46. 46.
    Austin, A., Fagan, D. G., & Mayhew, T. M. (1995). A stereological method for estimating the total number of ventricular myocyte nuclei in fetal and postnatal hearts. Journal of Anatomy, 187(Pt 3), 641–647.PubMedGoogle Scholar
  47. 47.
    Mandarim-de-Lacerda, C. A., das Santos, M. B., Le Floch-Prigent, P., & Narcy, F. (1997). Stereology of the myocardium in human foetuses. Early Human Development, 48, 249–259.PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2012

Authors and Affiliations

  • Yasin Bayir
    • 1
    Email author
  • Zekai Halici
    • 2
  • Emre Karakus
    • 3
  • Abdulmecit Albayrak
    • 2
  • Irmak Ferah
    • 4
  • Esref Kabalar
    • 5
  • Osman Keles
    • 6
  • Mevlut Sait Keles
    • 7
  • Bunyami Unal
    • 6
  1. 1.Department of BiochemistryFaculty of Pharmacy, Ataturk UniversityErzurumTurkey
  2. 2.Department of PharmacologyFaculty of Medicine, Ataturk UniversityErzurumTurkey
  3. 3.Department of PharmacologyFaculty of Veterinary, Ataturk UniversityErzurumTurkey
  4. 4.Department of PharmacologyFaculty of Pharmacy, Ataturk UniversityErzurumTurkey
  5. 5.Department of PathologyEducation and Research HospitalErzurumTurkey
  6. 6.Department of HistologyFaculty of Medicine, Ataturk UniversityErzurumTurkey
  7. 7.Department of BiochemistryFaculty of Medicine, Ataturk UniversityErzurumTurkey

Personalised recommendations