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Interaction of physical training and chronic nitroglycerin treatment on blood pressure and plasma oxidant/antioxidant systems in rats

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Abstract

Many individuals with cardiovascular diseases undergo periodic physical conditioning with or without medication. Therefore, this study investigated the interaction of exercise training and chronic nitroglycerin treatment on blood pressure (BP) and alterations in nitric oxide (NO), glutathione (GSH), antioxidant enzyme activities and lipid peroxidation in rats. Fisher 344 rats were divided into four groups: (1) sedentary control, (2) exercise training for 8 weeks, (3) nitroglycerin (15 mg/kg, s.c. for 8 weeks) and (4) training + nitroglycerin for 8 weeks. BP, heart rate (HR) and respiratory exchange ratio (RER) were monitored weekly for 8 weeks using tail-cuff method and oxygen/carbon dioxide analyzer, respectively. The animals were sacrificed 24 h after last treatments and plasma isolated and analyzed using HPLC, ELISA and UV-VIS spectrophotometric techniques. The results show that exercise conditioning significantly enhanced NO production (p < 0.001), GSH levels (p < 0.001), GSH/GSSG ratio (p < 0.05) and the up-regulation of the activities of catalase (CAT) (p < 0.05), glutathione peroxidase (GSH-Px) (p < 0.001), and glutathione reductase (GR) (p < 0.05), and depression of lactate levels (p < 0.001) in the plasma of the rat. These biochemical changes were accompanied by a significant increase in RER (p < 0.001) without a significant change in BP and HR. Chronic nitroglycerin administration significantly increased NO levels (p < 0.05), GSH levels (p < 0.001), superoxide dismutase (SOD) activity (p < 0.05), GST activity (p < 0.05), and decreased MDA levels (p < 0.05). These biochemical changes were accompanied by a significant decrease in BP (p < 0.05) and without any significant changes in HR and RER. Interaction of exercise training and chronic nitroglycerin treatment resulted in normalization of plasma NO, MDA, lactate levels, and CAT activity. The combination of exercise and nitroglycerin significantly enhanced GSH levels (p < 0.05), and the up-regulation of SOD (p < 0.001), GSH-Px (p < 0.05), GR (p < 0.05) and GST (p < 0.001) activities. These biochemical changes were accompanied by normalization of BP and a significant increased in RER (p < 0.001). The data suggest that the interaction of physical training and chronic nitroglycerin treatment resulted in the maintenance of BP and the up-regulation of plasma antioxidant enzyme activities and GSH levels in the rat.

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References

  1. Belch JJF, Bridges AB, Scott N, Chopra M: Oxygen free radicals and congestive heart failure. Br Heart J 65: 245-248, 1991

    Google Scholar 

  2. Somani SM, Husain K: Influence of exercise induced oxidative stress on the central nervous system. In: C.K. Sen, L. Packer, O. Hanninen (eds). Hand Book of Oxidants and Antioxidants in Exercise, 2nd edn. Elsevier Science B.V., Amsterdam, 2000, pp 713-754

    Google Scholar 

  3. Das UN: Free radicals, cytokines and nitric oxide in cardiac failure and myocardial infarction. Mol Cell Biochem 215: 145-152, 2000

    Google Scholar 

  4. Sagar S, Kallo IJ, Kaul N, Ganguly NK, Sharma, BK: Oxygen free radicals in essential hypertension. Mol Cell Biochem 111: 103-108, 1992

    Google Scholar 

  5. Davies JJA, Qintanilha AT, Brooks GA, Packer L: Free radicals and tissue damage produced by exercise. Biochem Biophys Res Commun 107: 1198-1205, 1982

    Google Scholar 

  6. Powers SK, Criswell D, Lawler J, Martin D, Lieu F, Ji LL, Herb RA: Rigorous exercise training increases superoxide dismutase activity in ventricular myocardium. Am J Physiol 265: 2094-2098, 1993

    Google Scholar 

  7. Somani SM, Rybak, LP, Frank S: Effect of acute and trained exercise on antioxidant system in rat heart subcellular fraction. Pharmacol Biochem Behav 51: 627-634, 1995

    Google Scholar 

  8. Somani SM, Husain K: Exercise training alters kinetics of antioxidant enzymes in rat tissues. Biochem Mol Biol Int 38: 587-595, 1996

    Google Scholar 

  9. Husain K, Somani SM: Response of exercise training and chronic ethanol ingestion on cardiac antioxidant system of rat. Alcohol 14: 301-307, 1997

    Google Scholar 

  10. Sessa WC, Pritchard K, Syedi N, Wang J, Hintze TH: Chronic exercise in dogs increases coronary vascular nitric oxide production and endothelial cell nitric oxide synthase gene expression. Circ Res 74: 349-353, 1993

    Google Scholar 

  11. Wang J, Wolin MS, Hintze TH: Chronic exercise enhances endothelium-mediated dilation of epicardial coronary artery in conscious dogs. Circ Res 73: 829-838, 1993

    Google Scholar 

  12. Rubanyi GM, Ho EH, Cantor EH, Inmma WC, Parker B: Cytoprotective function of nitric oxide: Inactivation of superoxide radicals produced by human leukocytes, Biochem Biophys Res Commun 181: 1392-1397, 1991

    Google Scholar 

  13. Tribulova N, Okruhlicova L, Bernatova I, Pechanova O: Chronic disturbances in NO production results in histochemical and subcellular alterations of the rat heart. Pysiol Res 49: 77-88, 2000

    Google Scholar 

  14. Pace B: Benefits of physical activity for the heart. J Am Med Assoc 285: 1536, 2001

    Google Scholar 

  15. Iemitsu M, Miyauchi T, Maeda S, Yuki K, Kobayashi T, Kumagai Y, Shimojo N, Yamaguchi I, Matsuda M: Intense exercise causes decrease in expression of both endothelial NO synthase and tissue Nox levels in hearts. Am J Physiol Reg Int Comp Physiol 279: R951-R959, 2000

    Google Scholar 

  16. Husain K: Exercise conditioning attenuates the hypertensive effects of nitric oxide synthase inhibitor in rat. Mol Cell Biochem 231: 129-137, 2002

    Google Scholar 

  17. Husain K, Hazelrigg SR: Oxidative injury due to chronic nitric oxide synthase inhibition in rat: effect of regular exercise on the heart. Biochim Biophys Acta 2002 (in press)

  18. De La Lande IS, Stafford I, Horowitz JD: Tolerance induction by transdermal glyceryl trinitrate in rats. Eur J Pharmacol 374: 71-75, 1999

    Google Scholar 

  19. Ma SX, Ignarro LJ, Byrns R, Li XY: Increased nitric oxide concentrations in posterior hypothalamus and central sympathetic function on nitrate tolerance following subcutaneous nitroglycerine. Nitric Oxide 3: 153-161, 1999

    Google Scholar 

  20. Sutton SC, Fung HL: Effect of dosage regimen on the development of tolerance to nitroglycerin in rats. J Cardiovasc Pharmacol 5: 1086-1092, 1983

    Google Scholar 

  21. Fariss WM, Reed DJ: High performance liquid chromatography of thiols and disulfides: Dinitrophenol derivatives. Meth Enzymol 143: 101-109, 1987

    Google Scholar 

  22. Misra HP, Fridovich I: The role of superoxide anion in the autoxidation of epinephrine and a simple assay for superoxide dismutase. J Biol Chem 243: 3170-3175, 1972

    Google Scholar 

  23. Aebi H: Catalase. Meth Enzymol 105: 125-126, 1984

    Google Scholar 

  24. Flohe LW, Gunzler A: Glutathione peroxidase. Meth Enzymol 105: 115-121, 1984

    Google Scholar 

  25. Carlberg L, Mannervik B: Glutathione reductase, Meth Enzymol 113: 484-499, 1985

    Google Scholar 

  26. Habig WH, Pabst MJ, Jakoby WB: Glutathione-s-transferases. The first step in mercapturic acid formation. J Biol Chem 249: 7130-7139, 1974

    Google Scholar 

  27. Ohkawa H, Ohishi N, Yagi K: Assay for lipid peroxides in animal and tissues by thiobarbituric acid reaction. Anal Biochem 95: 351-358, 1979

    Google Scholar 

  28. Read SM, Northcole DH: Minimization of variation in the response to different protein of the Coomassie blue G-dye-binding assay for protein. Anal Biochem 116: 53-64, 1981

    Google Scholar 

  29. Levy WC, Cerqueira MD, Harp GD, Johannessen K, Abrass IB, Schwartz RS, Stratton JR: Effect of endurance exercise training on heart rate variability at rest in healthy young and older men. Am J Cardiol 82: 1236-1241, 1998

    Google Scholar 

  30. Hickson RC, Hagberg JM, Ehsani, AA, Holloszy JO: Time course of adaptive responses of aerobic power and heart rate to training. Med Sci Sports Exerc 13: 17-20, 1981

    Google Scholar 

  31. Joyner MJ, Shastry S: Vascular endothelial growth factor and capillary density in exercise training. Exerc Sports Sci Rev 91: 97-98, 2000

    Google Scholar 

  32. Meister A, Anderson ME: Glutathione. Ann Rev Biochem 52: 711-722, 1991

    Google Scholar 

  33. Sen CK: Glutathione homeostasis in response to exercise training and nutritional supplements. Mol Cell Biochem 196: 31-42, 1999

    Google Scholar 

  34. Gore M, Feibig R, Hollander J, Leeuwenburgh C, Ohno H, Ji LL: Endurance training alters antioxidant enzyme gene expression in rat skeletal muscle. Can J Physiol Pharmacol 76: 1339-1345, 1998

    Google Scholar 

  35. Wang EQ, Lee WI, Fung HL: Lack of critical involvement of endothelial nitric oxide synthase in vascular nitrate tolerance in mice. Br J Pharmacol 135: 299-302, 2002

    Google Scholar 

  36. Fink B, Dikalov S, Bassenge E: A new approach for extracellular spin trapping of nitroglycerin-induced superoxide radicals both in vitro and in vivo. Free Radic Biol Med 28: 121-128, 2000

    Google Scholar 

  37. Yamamoto T, Bing RJ: Nitric oxide donors. Proc Soc Exp Biol Med 225: 200-206, 2000

    Google Scholar 

  38. Huang M, Manning RD, LeBlance MH, Hester RL: Overall haemodynamic studies after the chronic inhibition of endothelial-derived nitric oxide in rats. Am J Hypertens 8: 358-364, 1995

    Google Scholar 

  39. Rahman A, Ahmad S, Khan N, Sultana S, Athar M: Glyceryl trinitrate, a nitric oxide donor, suppresses renal oxidant damage caused by potassium bromate. Redox Rep 4: 263-269, 1999

    Google Scholar 

  40. Alin P, Danielson UH, Mannervik B: 4-hydroxyalk-2-enals are substrates for glutathione transferase. FEBS Lett 178: 267-270, 1985

    Google Scholar 

  41. Singhal SS, Piper JT, Srivastava SK, Chaubey M, Bandrowicz-Pikula J, Awasthi S, Awasthi YC: Rabbit Aorta glutathione-s-transferase and their role in bioactivation of trinitroglycerin. Toxicol Appl Pharmacol 140: 378-386, 1996

    Google Scholar 

  42. Vaziri ND, Wang XQ, Oveisi F, Rad B: Induction of oxidative stress by glutathione depletion causes severe hypertension in normal rats. Hypertension. 36: 142-146, 2000

    Google Scholar 

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Husain, K., Somani, S.M., Boley, T.M. et al. Interaction of physical training and chronic nitroglycerin treatment on blood pressure and plasma oxidant/antioxidant systems in rats. Mol Cell Biochem 247, 37–44 (2003). https://doi.org/10.1023/A:1024112532382

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