Effects of Captopril on Myocardial Oxidative Stress Changes in Post-Mi Rats

  • Neelam Khaper
  • Michael F. Hill
  • Julieta Pichardo
  • Pawan K. Singal
Part of the Progress in Experimental Cardiology book series (PREC, volume 2)


Changes in oxidative stress as indicated by the redox ratio as well as lipid peroxidation were characterized in rat hearts at different time points, subsequent to myocardial infarction (MI). In the severe heart failure stage at 16 weeks of post-MI, oxidative stress was significantly increased. Treatment with afterload reducing drugs, captopril or prazosin, started at 4 weeks post-MI and continued up to 16 weeks, resulted in a significant modulation of the oxidative stress changes with an improved hemodynamic function. It is suggested that the improved prognosis in MI patients with afterload reduction reported earlier may involve an improvement of the antioxidant reserve coupled with a reduction in the oxidative stress in the infarcted heart.


Sham Control Redox Ratio Afterload Reduction Hemodynamic Function GSSG Content 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


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  1. 1.
    Bolli R. 1988. Oxygen-derived free radicals and postischemic myocardial dysfunction (“Stunned Myocardium”). J Am Coll Cardiol 12:239–249.PubMedCrossRefGoogle Scholar
  2. 2.
    Siveski-Iliskovic N, Kaul N, Singal PK. 1994. Probucol promotes endogenous antioxidants and provides protection against adriamycin-induced cardiomyopathy in rats. Circulation 89:2829–2835.PubMedCrossRefGoogle Scholar
  3. 3.
    Dhalla AK, Singal PK. 1994. Antioxidant changes in hypertrophied and failing guinea pig hearts. Am J Physiol 266(Heart & Circ Physiol 36):H1280–H1285.PubMedGoogle Scholar
  4. 4.
    Singh N, Dhalla AK, Seneviratne CK, Singal PK. 1995. Oxidative stress and heart failure. Mol Cell Biochem 147:77–81.PubMedCrossRefGoogle Scholar
  5. 5.
    Kaul N, Siveski-Iliskovic N, Hill M, Slezak J, Singal PK. 1993. Free radicals and the heart. J Pharmacol and Toxicol Meth 30:55–67.CrossRefGoogle Scholar
  6. 6.
    Kanter MM, Hamlin RL, Unverferth DV, Davis HW, Merola AJ. 1985. Effect of exercise training on antioxidant enzymes and cardiotoxicity of doxorubicin. J Appl Physiol 59:1298–1303.PubMedGoogle Scholar
  7. 7.
    Singal PK, Kirshenbaum LA. 1990. A relative deficit in antioxidant reserve may contribute in cardiac failure. Can J Cardiol 6:47–49.PubMedGoogle Scholar
  8. 8.
    Gupta M, Singal PK. 1989. Higher antioxidative capacity during a chronic stable heart hypertrophy. Circ Res 64:398–406.PubMedCrossRefGoogle Scholar
  9. 9.
    Hill MF, Singal PK. 1996. Antioxidant and oxidative stress changes during heart failure subsequent to myocardial infarction in rats. Am J Pathol 148:291–300.PubMedGoogle Scholar
  10. 10.
    Khaper N, Singal PK. 1997. Effects of afterload reducing drugs on the pathogenesis of antioxidant changes and congestive heart failure in rats. J Am Coll Cardiol 219:856–861.CrossRefGoogle Scholar
  11. 11.
    Selye H, Bajusz E, Grasso S, Mendell P. 1960. Simple techniques for the surgical occlusion of coronary vessels in the rat. Angiology 11:398–407.PubMedCrossRefGoogle Scholar
  12. 12.
    Dixon IMC, Hata T, Dhalla NS. 1992. Sarcolemmal calcium transport in congestive heart failure due to myocardial infarction in rats. Am J Physiol 262:H1387–H1394.PubMedGoogle Scholar
  13. 13.
    Anderson ME. 1985. Determination of glutathione and glutathione disulfide in biological samples. Meth Enzymol 113:548–555.PubMedCrossRefGoogle Scholar
  14. 14.
    Singal PK, Pierce GN. 1986. Adriamycin stimulates low-affinity Ca2+-binding and lipid peroxidation but depresses myocardial function. Am J Physiol 250:H419–H425.PubMedGoogle Scholar
  15. 15.
    Pfeffer JM, Pfeffer MA, Braunwald E. 1985. Influence of chronic captopril therapy on the infarcted left ventricle of the rat. Circ Res 57:84–95.PubMedCrossRefGoogle Scholar
  16. 16.
    Jugdutt BI, Schwarz-Michorowski BL, Khan MI. 1992. Effects of long-term captopril therapy on left ventricular remodelling and function during healing in canine myocardial infarction. J Am Coll Cardiol 19:713–721.PubMedCrossRefGoogle Scholar
  17. 17.
    Pfeffer MA, Pfeffer JM, Steinberg C, Jinn P. 1985. Survival after an experimental myocardial infarction: Beneficial effects of long-term therapy with captopril. Circulation 72:406–412.PubMedCrossRefGoogle Scholar
  18. 18.
    Fantini GA, Yoshioka T. 1992. Use and limitations of thiobarbituric acid reaction to detect lipid peroxidation. Am J Physiol 263:H981–H982.PubMedGoogle Scholar
  19. 19.
    Weitz Z, Birnbaum AJ, Sobotka PA, Zarling EJ, Skosey JL. 1991. Elevated pentane levels during acute myocardial infarction. Lancet 337:933–935.PubMedCrossRefGoogle Scholar
  20. 20.
    McMurray J, Chopra M, Abdullah I, Smith WE, Dargie HJ. 1993. Evidence of oxidative stress in chronic heart failure in humans. Eur Heart J 14:1493–1498.PubMedCrossRefGoogle Scholar
  21. 21.
    Diaz-Velez CR, Garcia-Castineiras S, Mendoza RE, Hernandez-Lopez E. 1996. Increased malondialdehyde in peripheral blood of patients with congestive heart failure. Am Heart J 131:146–152.PubMedCrossRefGoogle Scholar
  22. 22.
    Charney RH, Levy DK, Kaiman J, Buchholz C, Ocampo ON, Eng C, Kukin ML. 1997. Free radical activity increases with NYHA class in congestive heart failure. J Am Coll Cardiol 102A, 930-159.Google Scholar
  23. 23.
    Jain SK, Levine SN. 1995. Elevated lipid peroxidation and vitamin E-quinone levels in heart ventricles of streptozotocin-treated diabetic rats. Free Rad Biol Med 18:337–341.PubMedCrossRefGoogle Scholar
  24. 24.
    Sobotka PA, Brottman MD, Weitz Z, Birnbaum, AJ, Skosey JL, Zarling EJ. 1993. Elevated breath pentane in heart failure reduced by free radical scavenger. Free Rad Biol Med 14:643–647.PubMedCrossRefGoogle Scholar
  25. 25.
    Chopra M, Scott N, McMurray J, Mclay J, Bridges A, Smith WE, Belch JJF. 1989. Captopril: A free radical scavenger. Br J Clin Pharmac 27:396–399.CrossRefGoogle Scholar
  26. 26.
    Reed DJ. 1990. Glutathione: Toxicological implications. Ann Rev Pharmacol Toxicol 30:603–631.CrossRefGoogle Scholar
  27. 27.
    Verma A, Hill M, Bhayana S, Pichardo J, Singal PK. 1997. Role of glutathione in acute myocardial adaptation. In Adaptation biology and medicine. Ed. BK Sharma, N Takeda, NK Ganguly, PK Singal. New Dehli: Narosa Publishers 1:399–408.Google Scholar
  28. 28.
    Bray TM, Taylor CG. 1993. Tissue glutathione, nutrition, and oxidative stress. Can J Physiol Pharmacol 71:746–751.PubMedCrossRefGoogle Scholar
  29. 29.
    Shan X, Aw TY, Jones DP. 1990. Glutathione dependent protection against oxidative injury. Pharmacol Ther 47:61–71.PubMedCrossRefGoogle Scholar
  30. 30.
    Dhalla AK, Hill M, Singal PK. 1996. Role of oxidative stress in the transition of hypertrophy to heart failure. J Am Coll Cardiol 28:506–514.PubMedCrossRefGoogle Scholar
  31. 31.
    Olson RD, Boerth RC, Gerber JG, Nies AS. 1981. Mechanism of adriamycin cardiotoxicity: Evidence for oxidative stress. Life Sciences 29:1393–1401.PubMedCrossRefGoogle Scholar
  32. 32.
    Kumar JS, Menon VP. 1992. Changes in levels of lipid peroxides and activity of Superoxide dismutase and catalase in diabetes associated with myocardial infarction. Indian J Exp Biol 30:122–127.PubMedGoogle Scholar

Copyright information

© Springer Science+Business Media New York 1998

Authors and Affiliations

  • Neelam Khaper
    • 1
    • 2
  • Michael F. Hill
    • 1
    • 2
  • Julieta Pichardo
    • 1
    • 2
  • Pawan K. Singal
    • 1
    • 2
  1. 1.Institute of Cardiovascular SciencesSt. Boniface General Hospital Research CentreCanada
  2. 2.Department of PhysiologyFaculty of Medicine University of ManitobaCanada

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