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Original Paper

Oxidative Stress and Renal Dysfunction in Salt-Sensitive Hypertension

Trolliet M.R. · Rudd M.A. · Loscalzo J.

Author affiliations

Whitaker Cardiovascular Institute, Evans Department of Medicine, Boston University School of Medicine, Boston, Mass., USA

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Kidney Blood Press Res 2001;24:116–123

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Article / Publication Details

First-Page Preview
Abstract of Original Paper

Published online: June 29, 2001
Issue release date: 2001

Number of Print Pages: 8
Number of Figures: 3
Number of Tables: 2

ISSN: 1420-4096 (Print)
eISSN: 1423-0143 (Online)

For additional information: https://www.karger.com/KBR

Abstract

Hypertension is a risk factor for the development of end-stage renal disease. The mechanisms underlying hypertensive nephropathy are poorly understood. There is evidence, however, that in hypertension there is an accumulation of partially reduced oxygen and its derivatives, known collectively as reactive oxygen species, which may contribute to progressive renal dysfunction. In the present study, we assess the contribution of oxidative stress in the development of salt-dependent hypertensive nephrosclerosis. Going beyond previous end point studies, which inferred renal function either indirectly or only qualitatively, we have determined oxidative stress concurrently with direct and quantitative measurements of renal function (via inulin and p-aminohippuric acid clearances). Moreover, in this time-dependent study, the measurements have been taken under low- as well as high-salt diets. As was expected from previous studies, in the Dahl salt-sensitive rat, a high-salt diet (8% NaCl) resulted in the development of hypertension, in a decreased glomerular filtration rate, and in a decreased renal plasma flow as compared with the normotensive control, the Dahl salt-resistant rat. In addition, however, we found clear evidence for the accumulation of reactive oxygen species in renal tissue homogenates of Dahl salt-sensitive rats on the high-salt diet. Our time-dependent protocol also indicated that renal oxidative stress follows, in time, the development of hypertension. We also found that after 2 weeks of increased salt loading, Dahl salt-sensitive rats excreted less cyclic guanosine monophosphate and NOx than Dahl salt-resistant rats on the same diet. It is known that urinary cyclic guanosine monophosphate and NOx represent the activity and stable derivatives of renal NO·, respectively, and that they closely correlate with renal vascular resistance. Therefore, our results suggest that, in the Dahl salt-sensitive rat, increased oxidative stress is associated with salt-dependent hypertensive nephrosclerosis and that decreased NO· bioavailability may represent a common factor responsible for the vascular and glomerular dysfunction.

© 2001 S. Karger AG, Basel


References

  1. Valderrábano F, Gómez-Camperrá F, Jones EH: Hypertension as a cause of end-stage renal disease: Lessons from international registries. Kidney Int Suppl 1998;68:60–66.
  2. Brown MA, Whitworth JA: Hypertension in human renal disease. J Hypertens 1992;10:701–712.
    External Resources
  3. Ferguson R, Grim CE, Opgenorth TJ: The epidemiology of end-state renal disease: The six-year South-Central Los Angeles experience, 1980–85. Am J Public Health 1987;77:864–865.
    External Resources
  4. Feldman HI, Klag MJ, Chiapella AP, Whelton PK: End-stage renal disease in US minority groups. Am J Kidney Dis 1992;19:397–410.
  5. Brancati FL, Whelton PK, Whittle JC, Klag MJ: Epidemiologic analysis of existing data to investigate hypertensive renal disease: An example from the Maryland End-Stage Renal Disease Registry. Am J Kidney Dis 1993;21 (suppl 1):15–24.
  6. US Renal Data System, USRD 1994 Annual Data Report. Am J Kidney Dis 1994;24(suppl 2):1–181.
  7. US Renal Data System, USRD 1999 Annual Data Report. Chapter II: Incidence and prevalence of ESRD. http://www.usrds.org/adr_1999. htm, pp 25–38.
  8. Perneger TV, Klag MJ, Feldman HI, Whelton PK: Projections of hypertension-related renal disease in middle-aged residents of the United States. JAMA 1993;269:1272–1277.
  9. Qualheim RE, Rostand SG, Kirk KA, Rutsky EA, Luke RG: Changing patterns of end-stage renal disease due to hypertension. Am J Kidney Dis 1991;18:336–343.
  10. Klag MJ, Whelton PK, Randall BL, Neaton JD, Brancati FL, Stamler J: End-stage renal disease in African-American and white men: 16-year MRFIT findings. JAMA 1997;277:1293–1298.
  11. Ichikawa I, Kiyama S, Yoshioka T: Renal antioxidant enzymes: Their regulation and function. Kidney Int 1994;45:1–9.
  12. Galat JA, Robinson AV, Rhodes RS: Oxygen free radical mediated renal dysfunction. J Surg Res 1989;46:520–525.
    External Resources
  13. Paller MS, Hoidal JR, Ferris TF: Oxygen free radicals in ischemic acute renal failure in the rat. J Clin Invest 1984;74:1156–1164.
  14. Chen PY, Sanders PW: Role of nitric oxide synthesis in salt-sensitive hypertension in Dahl/Rapp rats. Hypertension 1993;22:812–818.
  15. Reyes AA, Purkerson ML, Karl I, Klahr S: Dietary supplementation with L-arginine ameliorates the progression of renal disease in rats with subtotal nephrectomy. Am J Kidney Dis 1992;20:168–176.
  16. Reyes AA, Karl IE, Kissane J, Klahr S: L-Arginine administration prevents glomerular hyperfiltration and decreases proteinuria in diabetic rats. J Am Soc Nephrol 1993;4:1039–1045.
  17. Nakazono K, Watanabe N, Matsuno K, Saski J, Sato T, Inoue M: Does superoxide underlie the pathogenesis of hypertension? Proc Natl Acad Sci USA 1991;88:10045–10048.
  18. Uehara Y, Kawabata Y, Shirahase H, Wada K, Hashizume Y, Morishita S, Numabe A, Iwai J: Oxygen radical scavengers and renal protection by indapamide diuretic in salt-induced hypertension of Dahl strain rats. J Cardiovasc Pharmacol 1993;22(suppl 6):42–46.
  19. Gonick HC, Cohen AH, Ren Q, Saldanha LF, Khalil-Manesh F, Anzalone J, Sun YY: Effect of 2,3-dimercaptosuccinic acid on nephrosclerosis in the Dahl rat. I. Role of reactive oxygen species. Kidney Int 1996;50:1572–1581.
    External Resources
  20. Schnackenberg CG, Welch WJ, Wilcox CS: Normalization of blood pressure and renal vascular resistance in SHR with a membrane-permeable superoxide dismutase mimetic: Role of nitric oxide. Hypertension 1998;32:59–64.
  21. Schnackenberg CG, Wilcox CS: Two-week administration of tempol attenuates both hypertension and renal excretion of 8-iso prostaglandin F2. Hypertension 1999;33:424–428.
  22. Reckelhoff JE, Kanji V, Racusen LC, Schmidt AM, Yan SD, Morrow J, Roberts LJ, Salahudeen AK: Vitamin E ameliorates enhanced renal lipid peroxidation and accumulation of F2-isoprostanes in aging kidneys. Am J Physiol 1998;274:R767–R774.
    External Resources
  23. Reckelhoff JE, Hennington BS, Kanji V, Racusen LC, Schmidt AM, Yan SD, Morrow J, Roberts LJ, Salahudeen AK: Chronic aminoguanidine attenuatees renal dysfunction and injury in aging rats. Am J Hypertens 1999;12:492–498.
  24. Lowry OH, Rosebrough NJ, Farr L, Randall RJ: Protein measurement with the Folin phenol reagent. J Biol Chem 1951;193:265–275.
  25. Keaney JFJ, Xu A, Cunningham D, Jackson T, Frei B, Vita JA: Dietary probucol preserves endothelial function in cholesterol-fed rabbits by limiting vascular oxidative stress and superoxide generation. J Clin Invest 1995;95:2520–2529.
  26. Ohara Y, Peterson TE, Harrison DG: Hypercholesterolemia increases endothelial superoxide anion production. J Clin Invest 1993;91:2546–2551.
  27. Misko TP, Schilling RJ, Salvemini D, Moore WM, Currie MG: A fluorometric assay for the measurement of nitrite in biological samples. Anal Biochem 1993;214:11–16.
  28. Jackson TS, Lerner E, Weisbrod RM, Tajima M, Loscalzo J, Keaney JFJ: The vasodilatory properties of recombinant maxadilan. Am J Physiol 1996;271:H924–H930.
    External Resources
  29. Liu T-Z, Stern A, Morrow JD: The isoprostanes: Unique bioactive products of lipid peroxidation. J Biomed Sci 1998;5:415–420.
  30. Liochev SI, Fridovich I: Lucigenin luminescence as a measure of intracellular superoxide dismutase activity in Escherichia coli. Proc Natl Acad Sci USA 1997;94:2891–2896.
  31. Liochev SI, Fridovich I: Lucigenin as mediator of superoxide production: Revisited. Free Radic Biol Med 1998;26:777–778.
  32. Afanas’ev IB, Ostrachovitch EA, Korkina LG: Lucigenin is a mediator of cytochrome c reduction but not of superoxide production. Arch Biochem Biophys 1999;366:267–274.
  33. Simchon S, Manger W, Blumberg G, Brensliver J, Cortell S: Impaired renal vasodilation and urinary cGMP excretion in Dahl salt-sensitive rats. Hypertension 1996;27:653–657.
  34. Diederich D, Skopec J, Diederich A, Dai FX: Endothelial dysfunction in mesenteric resistance arteries of diabetic rats: Role of free radicals. Am J Physiol 1994;266:H1153–H1161.
    External Resources
  35. Tesfamariam B: Free radicals in diabetic endothelial cell dysfunction. Free Radic Biol Med 1994;16:383–391.
  36. McIntyre M, Bohr DF, Dominiczak AF: Endothelial function and hypertension: The role of superoxide anion. Hypertension 1999;34:539–545.
  37. Chen PY, Sanders PW: L-Arginine abrogates salt-sensitive hypertension in Dahl/Rapp rats. J Clin Invest 1991;88:1559–1567.
  38. Sanders PW: L-Arginine and arginine analogs in progressive renal failure. Blood Purif 1995;13:219–227.
    External Resources
  39. Baylis C, Mitruka B, Deng A: Chronic blockade of nitric oxide synthesis in the rat produces systemic hypertension and glomerular damage. J Clin Invest 1992;90:278–281.
  40. Salazar FJ, Pinilla JM, López F, Romero JC, Quesada T: Renal effects of prolonged synthesis inhibition of endothelium-derived nitric oxide. Hypertension 1992;20:113–117.
  41. Oliveira Ribeiro M, Antunes E, de Nucci G, Lovisolo SM, Zats R: Chronic inhibition of nitric oxide synthesis: A new model of arterial hypertension. Hypertension 1992;20:298–303.
  42. Ceriello A, Giugliano D, Quatraro A, Lefebvre PJ: Antioxidants show anti-hypertensive effect in diabetic and hypertensive subjects. Clin Sci 1991;81:739–742.
    External Resources
  43. Rajagopalan S, Kurz S, Münzel T, Tarpey M, Freeman BA, Griendling K, Harrison DG: Angiotensin II-mediated hypertension in the rat increases vascular superoxide production via membrane NADH/NADPH oxidase activation. J Clin Invest 1996;97:1916–1923.
    External Resources
  44. Halliwell B, Grootveld M: The measurements of free radical reactions in humans. FEBS Lett 1987;21:9–14.
  45. Lüscher TF, Raij L, Vanhoutte PM: Endothelium-dependent vascular responses in normotensive and hypertensive Dahl rats. Hypertension 1987;9:157–163.
    External Resources
  46. Shultz PJ, Tolins JP: Adaptation to increased dietary salt intake in the rat: Role of endogenous nitric oxide. J Clin Invest 1993;91:642–650.
  47. Murad F: Cyclic guanosine monophosphate as a mediator of vasodilation. J Clin Invest 1986;78:1–5.
  48. Davies M, Coles GA, Thomas GJ, Martin J, Lovett DH: Proteinases and the glomerulus: Their role in glomerular diseases. Klin Wochenschr 1990;68:1145–1149.
  49. Romero JC, Lahera V, Salom MG, Biondi ML: Role of the endothelium-dependent relaxing factor nitric oxide on renal function. J Am Soc Nephrol 1992;2:1371–1387.
  50. Tolins JP, Palmer RMJ, Moncada S, Raij L: Role of endothelium-derived relaxing factor in regulation of renal hemodynamic responses. Am J Physiol 1990;258:H655–H662.
    External Resources
  51. Ni Z, Oveisi F, Vaziri ND: Nitric oxide synthase isotype expression in salt-sensitive and salt-resistant Dahl rats. Hypertension 1999;34:552–557.
  52. Hayakawa H, Raij L: Nitric oxide synthase activity and renal injury in genetic hypertension. Hypertension 1998;31:266–270.
    External Resources

Article / Publication Details

First-Page Preview
Abstract of Original Paper

Published online: June 29, 2001
Issue release date: 2001

Number of Print Pages: 8
Number of Figures: 3
Number of Tables: 2

ISSN: 1420-4096 (Print)
eISSN: 1423-0143 (Online)

For additional information: https://www.karger.com/KBR


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