Skip to main content

Advertisement

Log in

Systemic antioxidant properties of L-carnitine in two different models of arterial hypertension

  • Original Paper
  • Published:
Journal of Physiology and Biochemistry Aims and scope Submit manuscript

Abstract

In spite of a wide range of drugs being available in the market, treatment of arterial hypertension still remains a challenge, and new therapeutic strategies could be developed in order to improve the rate of success in controlling this disease. Since oxidative stress has gained importance in the last few years as one of the mechanisms involved in the origin and development of hypertension, and considering that L-carnitine (LC) is a useful compound in different pathologies characterized by increased oxidative status, the aim of the present study was to investigate the systemic antioxidant effect of LC and its correlation to blood pressure in two experimental models of hypertension: (1) spontaneously hypertensive rats (SHR) and (2) rats with hypertension induced by Nω-nitro-L-arginine methyl ester (L-NAME). Treatment with captopril was also performed in SHR in order to compare the antioxidant and antihypertensive effects of LC and captopril. The antioxidant defense capacity, in terms of antioxidant enzyme activity, glutathione system availability and plasma total antioxidant capacity, was measured in both animal models with or without an oral, chronic treatment with LC. All the antioxidant parameters studied were diminished in SHR and in L-NAME-treated animals, an alteration that was in general reversed after treatments with LC and captopril. In addition, LC produced a significant but not complete reduction of systolic and diastolic blood pressure levels in these two models of hypertension, whereas captopril was able to normalize blood pressure. Both LC and captopril prevented the reduction in nitric oxide (NO) levels observed in hypertensive animals. This suggests a decrease in the systemic oxidative stress and a higher availability of NO induced by LC in a similar way to captopril’s effects, which could be relevant in the management of arterial hypertension eventually.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4

Similar content being viewed by others

References

  1. Arthur JR, Boyne R (1985) Superoxide dismutase and glutathione peroxidase activities in neutrophils from selenium deficient and copper deficient cattle. Life Sci 36:1569–1575

    Article  CAS  PubMed  Google Scholar 

  2. Berry C, Brosnan MJ, Fennell J, Hamilton CA, Dominiczak AF (2001) Oxidative stress and vascular damage in hypertension. Curr Opin Nephrol Hypertens 10:247–255

    Article  CAS  PubMed  Google Scholar 

  3. Bolterman RJ, Manriquez MC, Ortiz Ruiz MC, Juncos LA, Romero JC (2005) Effects of captopril on the renin angiotensin system, oxidative stress, and endothelin in normal and hypertensive rats. Hypertension 46:943–947

    Article  CAS  PubMed  Google Scholar 

  4. Bravo Y, Quiroz Y, Ferrebuz A, Vaziri ND, Rodriguez-Iturbe B (2007) Mycophenolate mofetil administration reduces renal inflammation, oxidative stress, and arterial pressure in rats with lead-induced hypertension. Am J Physiol Ren Physiol 293:F616–F623

    Article  CAS  Google Scholar 

  5. Cao G, Prior RL (1999) Measurement of oxygen radical absorbance capacity in biological samples. Meth Enzymol 299:50–62

    Article  CAS  PubMed  Google Scholar 

  6. Carlberg I, Mannervik B (1975) Purification and characterization of the flavoenzyme glutathione reductase from rat liver. J Biol Chem 250:5475–5480

    CAS  PubMed  Google Scholar 

  7. Cediel E, Sanz-Rosa D, Oubina MP, Heras N de las, Gonzalez Pacheco FR, Vegazo O, Jimenez J, Cachofeiro V, Lahera V (2003) Effect of AT1 receptor blockade on hepatic redox status in SHR: possible relevance for endothelial function? Am J Physiol Regul Integr Comp Physiol 285:R674–R681

    PubMed  Google Scholar 

  8. Dayanandan A, Kumar P, Panneerselvam C (2001) Protective role of L-carnitine on liver and heart lipid peroxidation in atherosclerotic rats. J Nutr Biochem 12:254–257

    Article  CAS  PubMed  Google Scholar 

  9. de Cavanagh EM, Inserra F, Ferder L, Fraga CG (2000) Enalapril and captopril enhance glutathione-dependent antioxidant defenses in mouse tissues. Am J Physiol Regul Integr Comp Physiol 278:R572–R577

    PubMed  Google Scholar 

  10. Dincer Y, Sekercioglu N, Pekpak M, Gunes KN, Akcay T (2008) Assessment of DNA oxidation and antioxidant activity in hypertensive patients with chronic kidney disease. Ren Fail 30:1006–1011

    Article  CAS  PubMed  Google Scholar 

  11. Duarte J, Jimenez R, O'Valle F, Galisteo M, Perez-Palencia R, Vargas F, Perez-Vizcaino F, Zarzuelo A, Tamargo J (2002) Protective effects of the flavonoid quercetin in chronic nitric oxide deficient rats. J Hypertens 20:1843–1854

    Article  CAS  PubMed  Google Scholar 

  12. Famularo G, De SC, Trinchieri V, Mosca L (2004) Carnitines and its congeners: a metabolic pathway to the regulation of immune response and inflammation. Ann N Y Acad Sci 1033:132–138

    Article  CAS  PubMed  Google Scholar 

  13. Ferrari R, Merli E, Cicchitelli G, Mele D, Fucili A, Ceconi C (2004) Therapeutic effects of L-carnitine and propionyl-L-carnitine on cardiovascular diseases: a review. Ann N Y Acad Sci 1033:79–91

    Article  CAS  PubMed  Google Scholar 

  14. Gomez-Amores L, Mate A, Miguel-Carrasco JL, Jimenez L, Jos A, Camean AM, Revilla E, Santa-Maria C, Vazquez CM (2007) L-carnitine attenuates oxidative stress in hypertensive rats. J Nutr Biochem 18:533–540

    Article  CAS  PubMed  Google Scholar 

  15. Gomez-Amores L, Mate A, Revilla E, Santa-Maria C, Vazquez CM (2006) Antioxidant activity of propionyl-L-carnitine in liver and heart of spontaneously hypertensive rats. Life Sci 78:1945–1952

    Article  CAS  PubMed  Google Scholar 

  16. Gonzalez W, Fontaine V, Pueyo ME, Laquay N, Messika-Zeitoun D, Philippe M, Arnal JF, Jacob MP, Michel JB (2000) Molecular plasticity of vascular wall during N(G)-nitro-L-arginine methyl ester-induced hypertension: modulation of proinflammatory signals. Hypertension 36:103–109

    CAS  PubMed  Google Scholar 

  17. Hamilton CA (2004) Strategies to reduce oxidative stress in cardiovascular disease. Clin Sci (Lond) 106:219–234

    Article  CAS  Google Scholar 

  18. Irat AM, Aktan F, Ozansoy G (2003) Effects of L-carnitine treatment on oxidant/antioxidant state and vascular reactivity of streptozotocin-diabetic rat aorta. J Pharm Pharmacol 55:1389–1395

    Article  CAS  PubMed  Google Scholar 

  19. Ito H, Torii M, Suzuki T (1992) A comparative study on defense systems for lipid peroxidation by free radicals in spontaneously hypertensive and normotensive rat myocardium. Comp Biochem Physiol B 103:37–40

    Article  CAS  PubMed  Google Scholar 

  20. Izgut-Uysal VN, Agac A, Derin N (2003) Effect of L-carnitine on carrageenan-induced inflammation in aged rats. Gerontology 49:287–292

    Article  PubMed  Google Scholar 

  21. Kalaiselvi T, Panneerselvam C (1998) Effect of L-carnitine on the status of lipid peroxidation and antioxidants in aging rats. J Nutr Biochem 9:575–581

    Article  CAS  Google Scholar 

  22. Kataoka C, Egashira K, Ishibashi M, Inoue S, Ni W, Hiasa K, Kitamoto S, Usui M, Takeshita A (2004) Novel anti-inflammatory actions of amlodipine in a rat model of arteriosclerosis induced by long-term inhibition of nitric oxide synthesis. Am J Physiol Heart Circ Physiol 286:H768–H774

    Article  CAS  PubMed  Google Scholar 

  23. Kitamoto S, Egashira K, Kataoka C, Usui M, Koyanagi M, Takemoto M, Takeshita A (2000) Chronic inhibition of nitric oxide synthesis in rats increases aortic superoxide anion production via the action of angiotensin II. J Hypertens 18:1795–1800

    Article  CAS  PubMed  Google Scholar 

  24. Landmesser U, Dikalov S, Price SR, McCann L, Fukai T, Holland SM, Mitch WE, Harrison DG (2003) Oxidation of tetrahydrobiopterin leads to uncoupling of endothelial cell nitric oxide synthase in hypertension. J Clin Invest 111:1201–1209

    CAS  PubMed  Google Scholar 

  25. Lassegue B, Griendling KK (2004) Reactive oxygen species in hypertension; an update. Am J Hypertens 17:852–860

    Article  CAS  PubMed  Google Scholar 

  26. Llorens S, Salazar FJ, Nava E (2005) Assessment of the nitric oxide system in the heart, aorta and kidney of aged Wistar-Kyoto and spontaneously hypertensive rats. J Hypertens 23:1507–1514

    Article  CAS  PubMed  Google Scholar 

  27. Mancia G et al (2007) 2007 Guidelines for the management of arterial hypertension: the task force for the management of arterial hypertension of the European society of hypertension (ESH) and of the european society of cardiology (ESC). J Hypertens 25:1105–1187

    Article  CAS  PubMed  Google Scholar 

  28. Marzinzig M, Nussler AK, Stadler J, Marzinzig E, Barthlen W, Nussler NC, Beger HG, Morris SM Jr, Bruckner UB (1997) Improved methods to measure end products of nitric oxide in biological fluids: nitrite, nitrate, and S-nitrosothiols. Nitric Oxide 1:177–189

    Article  CAS  PubMed  Google Scholar 

  29. Miguel-Carrasco JL, Mate A, Monserrat MT, Arias JL, Aramburu O, Vazquez CM (2008) The role of inflammatory markers in the cardioprotective effect of L-carnitine in L-NAME-induced hypertension. Am J Hypertens 21:1231–1237

    Article  CAS  PubMed  Google Scholar 

  30. Paglia DE, Valentine WN (1967) Studies on the quantitative and qualitative characterization of erythrocyte glutathione peroxidase. J Lab Clin Med 70:158–169

    CAS  PubMed  Google Scholar 

  31. Paravicini TM (2008) NADPH oxidases, reactive oxygen species, and hypertension: clinical implications and therapeutic possibilities. Diab Care 31(Suppl 2):S170–S180

    Article  CAS  Google Scholar 

  32. Pauly DF, Pepine CJ (2003) The role of carnitine in myocardial dysfunction. Am J Kidney Dis 41:S35–S43

    Article  CAS  PubMed  Google Scholar 

  33. Rajasekar P, Palanisamy N, Anuradha CV (2007) Increase in nitric oxide and reductions in blood pressure, protein kinase C beta II and oxidative stress by L-carnitine: a study in the fructose-fed hypertensive rat. Clin Exp Hypertens 29:517–530

    Article  CAS  PubMed  Google Scholar 

  34. Rauchova H, Dobesova Z, Drahota Z, Zicha J, Kunes J (1998) The effect of chronic L-carnitine treatment on blood pressure and plasma lipids in spontaneously hypertensive rats. Eur J Pharmacol 342:235–239

    Article  CAS  PubMed  Google Scholar 

  35. Redon J, Oliva MR, Tormos C, Giner V, Chaves J, Iradi A, Saez GT (2003) Antioxidant activities and oxidative stress byproducts in human hypertension. Hypertension 41:1096–1101

    Article  CAS  PubMed  Google Scholar 

  36. Rodriguez-Iturbe B, Zhan CD, Quiroz Y, Sindhu RK, Vaziri ND (2003) Antioxidant-rich diet relieves hypertension and reduces renal immune infiltration in spontaneously hypertensive rats. Hypertension 41:341–346

    Article  CAS  PubMed  Google Scholar 

  37. Samiec PS (1998) Glutathione in human plasma: decline in association with aging, age-related macular degeneration, and diabetes. Free Radic Biol Med 24:699–704

    Article  CAS  PubMed  Google Scholar 

  38. Sayed-Ahmed MM, Khattab MM, Gad MZ, Mostafa N (2001) L-carnitine prevents the progression of atherosclerotic lesions in hypercholesterolaemic rabbits. Pharmacol Res 44:235–242

    Article  CAS  PubMed  Google Scholar 

  39. Sener G, Paskaloglu K, Satiroglu H, Alican I, Kacmaz A, Sakarcan A (2004) L-carnitine ameliorates oxidative damage due to chronic renal failure in rats. J Cardiovasc Pharmacol 43:698–705

    Article  CAS  PubMed  Google Scholar 

  40. Simko F, Pechanova O, Pelouch V, Krajcirovicova K, Mullerova M, Bednarova K, Adamcova M, Paulis L (2009) Effect of melatonin, captopril, spironolactone and simvastatin on blood pressure and left ventricular remodelling in spontaneously hypertensive rats. J Hypertens 27(Suppl 6):S5-10–S5-10

    Google Scholar 

  41. Takemoto M, Egashira K, Usui M, Numaguchi K, Tomita H, Tsutsui H, Shimokawa H, Sueishi K, Takeshita A (1997) Important role of tissue angiotensin-converting enzyme activity in the pathogenesis of coronary vascular and myocardial structural changes induced by long-term blockade of nitric oxide synthesis in rats. J Clin Invest 99:278–287

    Article  CAS  PubMed  Google Scholar 

  42. Torok J (2008) Participation of nitric oxide in different models of experimental hypertension. Physiol Res 57:813–825

    CAS  PubMed  Google Scholar 

  43. Ulker S, McMaster D, McKeown PP, Bayraktutan U (2003) Impaired activities of antioxidant enzymes elicit endothelial dysfunction in spontaneous hypertensive rats despite enhanced vascular nitric oxide generation. Cardiovasc Res 59:488–500

    Article  CAS  PubMed  Google Scholar 

  44. Vescovo G, Ravara B, Gobbo V, Sandri M, Angelini A, Della BM, Dona M, Peluso G, Calvani M, Mosconi L, Dalla LL (2002) L-Carnitine: a potential treatment for blocking apoptosis and preventing skeletal muscle myopathy in heart failure. Am J Physiol Cell Physiol 283:C802–C810

    CAS  PubMed  Google Scholar 

  45. Vesela E, Racek J, Trefil L, Jankovy'ch V, Pojer M (2001) Effect of L-carnitine supplementation in hemodialysis patients. Nephron 88:218–223

    Article  CAS  PubMed  Google Scholar 

  46. Wilcox CS (2002) Reactive oxygen species: roles in blood pressure and kidney function. Curr Hypertens Rep 4:160–166

    Article  PubMed  Google Scholar 

  47. Yasunari K, Maeda K, Nakamura M, Yoshikawa J (2002) Oxidative stress in leukocytes is a possible link between blood pressure, blood glucose, and C-reacting protein. Hypertension 39:777–780

    Article  CAS  PubMed  Google Scholar 

  48. Yuan YV, Kitts DD (2002) Dietary fat source and cholesterol interactions alter plasma lipids and tissue susceptibility to oxidation in spontaneously hypertensive (SHR) and normotensive Wistar Kyoto (WKY) rats. Mol Cell Biochem 232:33–47

    Article  CAS  PubMed  Google Scholar 

  49. Yuan YV, Kitts DD, Godin DV (1998) Variations in dietary fat and cholesterol intakes modify antioxidant status of SHR and WKY rats. J Nutr 128:1620–1630

    CAS  PubMed  Google Scholar 

  50. Zhan CD, Sindhu RK, Pang J, Ehdaie A, Vaziri ND (2004) Superoxide dismutase, catalase and glutathione peroxidase in the spontaneously hypertensive rat kidney: effect of antioxidant-rich diet. J Hypertens 22:2025–2033

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgments

This work was supported by grants from Ministerio de Sanidad y Consumo, Instituto de Salud Carlos III, Fondo de Investigación Sanitaria (PI051026), and Consejería de Salud, Junta de Andalucía (PI-0034). The group is member of the Network for Cooperative Research on Membrane Transport Proteins (REIT), co-funded by the Spanish Ministerio de Educación y Ciencia and the European Regional Development Fund (ERDF; Grant BFU2007-30688-E/BFI). JL Miguel-Carrasco was supported by a research grant from Consejería de Salud, Junta de Andalucía (PI-0034).

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Alfonso Mate.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Mate, A., Miguel-Carrasco, J.L., Monserrat, M.T. et al. Systemic antioxidant properties of L-carnitine in two different models of arterial hypertension. J Physiol Biochem 66, 127–136 (2010). https://doi.org/10.1007/s13105-010-0017-7

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s13105-010-0017-7

Keywords

Navigation