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Contribution of mitochondrial function to exercise-induced attenuation of renal dysfunction in spontaneously hypertensive rats

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Abstract

It is well known that exercise training exhibits renal protective effects in animal models of hypertension and chronic renal failure. However, the mechanisms regulating these effects of exercise training remain unclear. This study aimed to investigate the role of mitochondrial function in exercise-induced attenuation of renal injury in spontaneously hypertensive rats (SHR). The adult male SHR and age-matched normotensive Wistar-Kyoto rats (WKY) were given moderate-intensity exercise for 12 weeks or treated with MitoQ10 for 8 weeks. In this work, exercise training in SHR reduced blood pressure, and effectively attenuated renal dysfunction, marked by reduced creatinine excretion, albuminuria, blood urea nitrogen, and glomerular sclerosis. Exercise training in SHR reduced MDA levels in plasma and kidneys and suppressed formation of 3-nitrotyrosine in kidneys. Exercise training suppressed mitochondrial ROS and \({\text{O}}_2^ - \) formation, enhanced ATP formation, reduced mitochondrial swelling, and restored electron transport chain enzyme activity in kidneys of SHR. Furthermore, exercise training upregulated protein expression of uncoupling protein 2 and manganese superoxide dismutase in kidneys of SHR. In addition, treatment with mitochondria-targeted antioxidant MitoQ10 exhibited similar renal protective effects in SHR. In conclusion, chronic aerobic exercise training preserved mitochondrial function and abated oxidative stress in the kidneys of SHR, which may in part explain the protective effect of exercise on renal function and structure in hypertensive individuals.

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References

  1. Kannel WB (2000) Review of recent Framingham study hypertension research. Curr Hypertens Rep 2:239–240

    Article  CAS  PubMed  Google Scholar 

  2. Hall ME, do Carmo JM, da Silva AA, Juncos LA, Wang Z, Hall JE (2014) Obesity, hypertension, and chronic kidney disease. Int J Nephrol Renovasc Dis 7:75–88

    Article  PubMed Central  PubMed  Google Scholar 

  3. Lamina S, Okoye CG, Hanif SM (2013) Randomised controlled trial: effects of aerobic exercise training programme on indices of adiposity and metabolic markers in hypertension. J Pak Med Assoc 63:680–687

    PubMed  Google Scholar 

  4. Lee LL, Watson MC, Mulvaney CA, Tsai CC, Lo SF (2010) The effect of walking intervention on blood pressure control: a systematic review. Int J Nurs Stud 47:1545–1561

    Article  PubMed  Google Scholar 

  5. Chang Y, Cheng SY, Lin M, Gau FY, Chao YF (2010) The effectiveness of intradialytic leg ergometry exercise for improving sedentary life style and fatigue among patients with chronic kidney disease: a randomized clinical trial. Int J Nurs Stud 47:1383–1388

    Article  PubMed  Google Scholar 

  6. Henrique DM, Reboredo Mde M, Chaoubah A, Paula RB (2010) Aerobic exercise improves physical capacity in patients under chronic hemodialysis. Arq Bras Cardiol 94:823–828

    Article  PubMed  Google Scholar 

  7. Odden MC (2010) Physical functioning in elderly persons with kidney disease. Adv Chronic Kidney Dis 17:348–357

    Article  PubMed  Google Scholar 

  8. Westhoff TH, Franke N, Schmidt S, Vallbracht-Israng K, Meissner R, Yildirim H, Schlattmann P, Zidek W, Dimeo F, van der Giet M (2007) Too old to benefit from sports? The cardiovascular effects of exercise training in elderly subjects treated for isolated systolic hypertension. Kidney Blood Press Res 30:240–247

    Article  PubMed  Google Scholar 

  9. Agarwal D, Elks CM, Reed SD, Mariappan N, Majid DS, Francis J (2012) Chronic exercise preserves renal structure and hemodynamics in spontaneously hypertensive rats. Antioxid Redox Signal 16:139–152

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  10. Garcia-Pinto AB, de Matos VS, Rocha V, Moraes-Teixeira J, Carvalho JJ (2011) Low-Intensity physical activity beneficially alters the ultrastructural renal morphology of spontaneously hypertensive rats. Clinics (Sao Paulo) 66:855–863

    Article  Google Scholar 

  11. Ciampone S, Borges R, de Lima IP, Mesquita FF, Cambiucci EC, Gontijo JA (2011) Long-term exercise attenuates blood pressure responsiveness and modulates kidney angiotensin II signalling and urinary sodium excretion in SHR. J Renin Angiotensin Aldosterone Syst 12:394–403

    Article  CAS  PubMed  Google Scholar 

  12. Balaban RS, Nemoto S, Finkel T (2005) Mitochondria, oxidants, and aging. Cell 120:483–495

    Article  CAS  PubMed  Google Scholar 

  13. de Cavanagh EM, Toblli JE, Ferder L, Piotrkowski B, Stella I, Inserra F (2006) Renal mitochondrial dysfunction in spontaneously hypertensive rats is attenuated by losartan but not by amlodipine. Am J Physiol Regul Integr Comp Physiol 290:R1616–1625

    Article  PubMed  Google Scholar 

  14. Piotrkowski B, Fraga CG, de Cavanagh EMV (2007) Mitochondrial function and nitric oxide metabolism are modified by enalapril treatment in rat kidney. Am J Physiol Regul Integr Comp Physiol 292:R1494–R1501

    Article  CAS  PubMed  Google Scholar 

  15. Husain K (2004) Physical conditioning modulates rat cardiac VEGF gene expression in nitric oxide–deficient hypertension. Biochem Biophys Res Commun 320:1169–1174

    Article  CAS  PubMed  Google Scholar 

  16. Gu Q, Wang B, Zhang XF, Ma YP, Liu JD, Wang XZ (2014) Contribution of renin-angiotensin system to exercise-induced attenuation of aortic remodeling and improvement of endothelial function in spontaneously hypertensive rats. Cardiovasc Pathol 23:298–305

    Article  CAS  PubMed  Google Scholar 

  17. Ogihara CA, Schoorlemmer GH, Levada AC, Pithon-Curi TC, Curi R, Lopes OU, Colombari E, Sato MA (2010) Exercise changes regional vascular control by commissural NTS in spontaneously hypertensive rats. Am J Physiol Regul Integr Comp Physiol 299:R291–297

    Article  CAS  PubMed  Google Scholar 

  18. Kimura K, Tojo A, Matsuoka H, Sugimoto T (1991) Renel arteriolar diameters in spontaneously hypertensive rats: vascular cast study. Hypertension 18:101–110

    Article  CAS  PubMed  Google Scholar 

  19. Elks CM, Mariappan N, Haque M, Guggilam A, Majid DS, Francis J (2009) Chronic NF-kB blockade reduces cytosolic and mitochondrial oxidative stress and attenuates renal injury and hypertension in SHR. Am J Physiol Renal Physiol 296:F298–305

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  20. Mariappan N, Soorappan RN, Haque M, Sriramula S, Francis J (2007) TNF-α-induced mitochondrial oxidative stress and cardiac dysfunction: restoration by superoxide dismutase mimetic Tempol. Am J Physiol Heart Circ Physiol 293:H2726–H2737

    Article  CAS  PubMed  Google Scholar 

  21. Maher P, Salgado KF, Zivin JA, Lapchak PA (2007) A novel approach to screening for new neuroprotective compounds for the treatment of stroke. Brain Res 1173:117–125

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  22. Wilcox CS (2005) Oxidative stress and nitric oxide deficiency in the kidney: a critical link to hypertension? Am J Physiol Regul Integr Comp Physiol 289:R913–R935

    Article  CAS  PubMed  Google Scholar 

  23. Ramachandran A, Levonen AL, Brookes PS, Ceaser E, Shiva S, Barone MC, Darley-Usmar V (2002) Mitochondria, nitric oxide, and cardiovascular dysfunction. Free Radic Biol Med 33:1465–1474

    Article  CAS  PubMed  Google Scholar 

  24. Friedman JR, Nunnari J (2014) Mitochondrial form and function. Nature 505:335–343

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  25. Calabrese V, Cornelius C, Cuzzocrea S, Iavicoli I, Rizzarelli E, Calabrese EJ (2011) Hormesis, cellular stress response and vitagenes as critical determinants in aging and longevity. Mol Aspects Med 32:279–304

    Article  CAS  PubMed  Google Scholar 

  26. Ralph SJ, Moreno-Sanchez R, Neuzil J, Rodriguez-Enriquez S (2011) Inhibitors of succinate, quinone reductase/Complex II regulate production of mitochondrial reactive oxygen species and protect normal cells from ischemic damage but induce specific cancer cell death. Pharm Res 28:2695–2730

    Article  CAS  PubMed  Google Scholar 

  27. Gu Q, Wang B, Zhang XF, Ma YP, Liu JD, Wang XZ (2014) Chronic aerobic exercise training attenuates aortic stiffening and endothelial dysfunction through preserving aortic mitochondrial function in aged rats. Exp Gerontol 56:37–44

    Article  CAS  PubMed  Google Scholar 

  28. Krauss S, Zhang CY, Lowell BB (2005) The mitochondrial uncoupling-protein homologues. Nat Rev Mol Cell Biol 6:248–261

    Article  CAS  PubMed  Google Scholar 

  29. Mattiasson G, Sullivan PG (2006) The emerging functions of UCP2 in health, disease, and therapeutics. Antioxid Redox Signal 8:1–38

    Article  CAS  PubMed  Google Scholar 

  30. Pi J, Bai Y, Daniel KW, Liu D, Lyght O, Edelstein D, Brownlee M, Corkey BE, Collins S (2009) Persistent oxidative stress due to absence of uncoupling protein 2 associated with impaired pancreatic beta-cell function. Endocrinology 150:3040–3048

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  31. Fukunaga Y, Itoh H, Hosoda K (2000) Doi K, Matsuda J, Son C, Yamashita J, Chun TH, Tanaka T, Inoue M, Masatsugu K, Saito T, Sawada N, Nakao K Altered gene expression of uncoupling protein-2 and -3 in stroke-prone spontaneously hypertensive rats. J Hypertens 18:1233–1238

    Article  CAS  PubMed  Google Scholar 

  32. Yoshida T, Kato K, Fujimaki T, Yokoi K, Oguri M, Watanabe S, Metoki N, Yoshida H, Satoh K, Aoyagi Y, Nishigaki Y, Tanaka M, Nozawa Y, Kimura G, Yamada Y (2009) Association of genetic variants with chronic kidney disease in Japanese individuals. Clin J Am Soc Nephrol 4:883–890

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  33. Tripathi G, Sharma RK, Baburaj VP, Sankhwar SN, Jafar T, Agrawal S (2008) Genetic risk factors for renal failure among north Indian ESRD patients. Clin Biochem 41:525–531

    Article  PubMed  Google Scholar 

  34. Di-Castro S, Scarpino S, Marchitti S, Bianchi F, Stanzione R, Cotugno M, Sironi L, Gelosa P, Duranti E, Ruco L, Volpe M, Rubattu S (2013) Differential modulation of uncoupling protein 2 in kidneys of stroke-prone spontaneously hypertensive rats under high-salt/low-potassium diet. Hypertension 61:534–541

    Article  CAS  PubMed  Google Scholar 

  35. Radi R, Cassina A, Hodara R, Quijano C, Castro L (2002) Peroxynitrite reactions and formation in mitochondria. Free Radic Biol Med 33:1451–1464

    Article  CAS  PubMed  Google Scholar 

  36. Falone S, D’Alessandro A, Mirabilio A, Cacchio M, Di Ilio C, Di Loreto S, Amicarelli F (2012) Late-onset running biphasically improves redox balance, energy- and methylglyoxal-related status, as well as SIRT1 expression in mouse hippocampus. PLoS ONE 7:e48334

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  37. Falone S, D’Alessandro A, Mirabilio A, Petruccelli G, Cacchio M, Di Ilio C, Di Loreto S, Amicarelli F (2012) Long term running biphasically improves methylglyoxal-related metabolism, redox homeostasis and neurotrophic support within adult mouse brain cortex. PLoS ONE 7:e31401

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  38. Liu J, Yeo HC, Overvik-Douki E, Hagen T, Doniger SJ, Chyu DW, Brooks GA, Ames BN (2000) Chronically and acutely exercised rats: biomarkers of oxidative stress and endogenous antioxidants. J Appl Physiol 89:21–28

    CAS  PubMed  Google Scholar 

  39. Ji LL (2008) Modulation of skeletal muscle antioxidant defense by exercise: role of redox signaling. Free Radic Biol Med 44:142–152

    Article  CAS  PubMed  Google Scholar 

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Conflict of interest

We declare that we have no conflict of interest.

Huamn and Animal Rights Statement

All studies involving animals in this work are reported in accordance with the ARRIVE guidelines for reporting experiments involving animals.

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Authors and Affiliations

  1. School of Physical Education, Xi’an Technological University, 4 Jinhua Road, Xi’an, 710032, Shaanxi Province, China

    Qi Gu

  2. School of Physical Education, Luoyang Normal University, Luoyang, Henan Province, China

    Li Zhao

  3. Department of Neurology, Chengyang People’s Hospital, Qingdao, Shandong Province, China

    Yan-Ping Ma

  4. Department of Gastroenterology, The Third People’s Hospital of Datong, Datong, Shanxi Province, China

    Jian-Dong Liu

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  1. Qi Gu
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  2. Li Zhao
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Correspondence to Qi Gu.

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Gu, Q., Zhao, L., Ma, YP. et al. Contribution of mitochondrial function to exercise-induced attenuation of renal dysfunction in spontaneously hypertensive rats. Mol Cell Biochem 406, 217–225 (2015). https://doi.org/10.1007/s11010-015-2439-6

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  • DOI: https://doi.org/10.1007/s11010-015-2439-6

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