Hypertension and Sodium/Lithium

Kidney International (1992) 41, 872–876; doi:10.1038/ki.1992.133

Lipids and cellular Na+/H+ antiport activity in diabetic nephropathy

Leong L Ng1 and Joan E Davies1

1Department of Pharmacology, Clinical Sciences Building, Leicester Royal Infirmary, Leicester, England, United Kingdom

Correspondence: Dr L L Ng, Department of Pharmacology, Clinical Sciences Building, Leicester Royal Infirmary, Leicester, LE2 7LX, England, United Kingdom

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Abstract

Lipids and cellular Na+/H+ antiport activity in diabetic nephropathy. Increased cellular Na+/H+ antiport activity has been documented in various cell types from hypertensive humans and rats. This membrane abnormality may be associated with the thickening of the vascular media of resistance vessels. Such an abnormality has also been demonstrated in cells from type I diabetic patients with nephropathy, and may indicate the predisposition to essential hypertension in such patients. We now demonstrate the importance of the rate-limiting enzyme for cholesterol and isoprenoid synthesis, 3-hydroxy-3-methyl-glutaryl coenzyme A reductase, in determining cellular Na+/H+ an-tiport activity. This finding may have application in the future treatment of diabetic patients with proteinuria.

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References

  1. Borch-Johnsen K, Andersen PK, Deckert T: The effect of proteinuria on relative mortality in Type 1 (insulin-dependent) diabetes mellitus. Diabetologia 28:590–596, 1985 | PubMed | ChemPort |
  2. Andersen AR, Christiansen JS, Andersen JK, Kreiner S, Deckert T: Diabetic nephropathy in Type 1 (insulin-dependent) diabetes: An epidemiological study. Diabetologia 25:496–501, 1983 | PubMed | ISI | ChemPort |
  3. Krolewski AS, Warram JH, Christlieb AR, Bunsick EJ, Kahn CR: The changing natural history of nephropathy in type 1 diabetes. Am J Med 78:785–794, 1985 | Article | PubMed | ISI | ChemPort |
  4. Deckert T, Poulson JE: Diabetic nephropathy: Fault or destiny? Diabetologia 21:178–183, 1981
  5. Mogensen CE, Christensen CK: Predicting diabetic nephropathy in insulin-dependent patients. N Engl J Med 311:89–93, 1984 | PubMed | ISI | ChemPort |
  6. Wiseman M, Viberti GC, Mackintosh D, Jarrett RJ, Keen H: Glycaemia, arterial pressure and micro-albuminuria in Type 1 (insulin-dependent) diabetes mellitus. Diabetologia 26:401–405, 1984
  7. Seaquist ER, Goetz FC, Rich S, Barbosa J: Familial clustering of diabetic kidney disease. N Engl J Med 320:1161–1165, 1989 | PubMed | ISI | ChemPort |
  8. Canessa M, Adragna N, Solomon HS, Connolly TM, Tosteson DC: Increased sodium-lithium countertransport in red cells of patients with essential hypertension. N Engl J Med 302:772–776, 1980 | PubMed | ISI | ChemPort |
  9. Hasstedt SJ, Wu LL, Ash KO, Kuida H, Williams R: Hypertension and sodium-lithium countertransport in Utah pedigrees: Evidence for major locus inheritance. Am J Hum Genet 43:14–22, 1988
  10. Krolewski AS, Canessa M, Warram JH, Laffel LMB, Christlieb AR, Knowler WC, Rand LI: Predisposition to hypertension and susceptibility to renal disease in insulin-dependent diabetes mellitus. N Engl J Med 318:140–145, 1988 | PubMed | ISI | ChemPort |
  11. Mangili R, Bending JJ, Scott G, Li LK, Gupta A, Viberti GC: Increased sodium-lithium countertransport activity in red cells of patients with insulin-dependent diabetes and nephropathy. N Engl J Med 318:146–150, 1988 | PubMed | ISI | ChemPort |
  12. Mahnensmith RL, Aronson PS: The plasma membrane sodium-hydrogen exchanger and its role in physiological and pathophysiological processes. Circ Res 56:773–788, 1985 | PubMed | ISI | ChemPort |
  13. Ng LL, Harker M, Abel ED: Mechanisms of leucocyte sodium influx in essential hypertension. Clin Sci 75:521–526, 1988
  14. Ng LL, Dudley C, Bomford J, Hawley D: Leucocyte intracellular pH and Na+/H+ antiport activity in human hypertension. J Hypertens 7:471–475, 1989
  15. Dudley CRK, Taylor DJ, Ng LL, Kemp GJ, Ratcliffe PJ, Radda GK, Ledingham JGG: Evidence for abnormal Na+/H+ antiport activity detected by phosphorus nuclear magnetic resonance spectroscopy in exercising skeletal muscle of patients with essential hypertension. Clin Sci 79:491–497, 1990
  16. Ng LL, Simmons D, Frighi V, Garrido MC, Bomford J, Hockaday TDR: Leucocyte Na+/H+ antiport activity in Type 1 (insulin-dependent) diabetic patients with nephropathy. Diabetologia 33:371–377, 1990 | Article | PubMed | ISI | ChemPort |
  17. Sardet C, Counillon L, Franchi A, Pouyssegur J: Growth factors induce phosphorylation of the Na+/H+ antiporter, a glycoprotein of 110 kD. Science 247:123–126, 1990
  18. Ng LL, Simmons D, Frighi V, Garrido MC, Bomford J: Effect of protein kinase C modulators on the leucocyte Na+/H+ antiport in Type 1 (insulin-dependent) diabetic subjects with albuminuria. Diabetologia 33:278–284, 1990
  19. Lee T-S, MacGregor LC, Fluharty SJ, King GL: Differential regulation of protein kinase C and (Na,K)-adenosine triphosphatase activities by elevated glucose levels in retinal capillary endothelial cells. J Clin Invest 83:90–94, 1989 | PubMed | ChemPort |
  20. Yusufi ANK, Szczepanska-Konkel M, Dousa TP: Role of N-linked oligosaccharides in the transport activity of the Na+/H+ antiporter in rat renal brush-border membrane. J Biol Chem 263:13683–13691, 1988
  21. Kornfeld R, Kornfeld S: Assembly of asparagine-linked oligosaccharides. Ann Rev Biochem 54:631–664, 1985 | Article | PubMed | ISI | ChemPort |
  22. MacMahon SW, MacDonald GJ, Blacket RB: Plasma lipoprotein levels in treated and untreated hypertensive men and women. Arteriosclerosis 5:391–396, 1985 | PubMed |
  23. Jones SL, Close CF, Mattock MB, Jarrett RJ, Keen H, Viberti GC: Plasma lipid and coagulation factor concentrations in insulin-dependent diabetics with microalbuminuria. Br Med J 298:487–490, 1989 | ISI | ChemPort |
  24. Jensen T, Stender S, Deckert T: Abnormalities in plasma concentrations of lipoproteins and fibrinogen in Type 1 (insulin-dependent) diabetic patients with increased urinary albumin excretion. Diabetologia 31:142–145, 1988 | Article | PubMed | ISI | ChemPort |
  25. Ononogbu IC, Lewis B: Lipoprotein fractionation by a precipitation method. A simple quantitative procedure. Clin Chim Acta 71:397–402, 1976
  26. De Figueiredo CEP, Ng LL, Davies JE, Cazana FJL, Hendry BM, Ellory JC: Effect of cell cholesterol on Na-H antiporter activity in human lymphoblasts. (abstract) J Physiol 432:26P, 1990
  27. Brown MS, Goldstein JL: Multivalent feedback regulation of HMG CoA reductase, a control mechanism coordinating isoprenoid synthesis and cell growth. J Lipid Res 21:505–517, 1980 | PubMed | ISI | ChemPort |
  28. Frighi V, Ng LL, Lewis A, Dhar H: Na+/H+ antiport and buffering capacity in human polymorphonuclear and mononuclear leucocytes. Clin Sci 80:95–99, 1991
  29. Goldstein JL, Brown MS: Regulation of the mevalonate pathway. Nature 343:425–430, 1990 | Article | PubMed | ISI | ChemPort |
  30. Ng LL, Davies JE: HMG CoA reductase inhibitors affect Na+/H+ antiport activity in human lymphoblasts. Am J Physiol 261:C780–C786, 1991
  31. Grundy SM: HMG-CoA reductase inhibitors for treatment of hypercholesterolemia. Engl J Med 319:24–33, 1988
  32. Weder AB, Serr C, Torretti BA, Bassett DR, Zweifler AJ: Effect of lovastatin treatment on red blood cell and platelet cation transport. Hypertension 17:203–209, 1991
  33. Kasiske BL, O'Donnell MP, Cowardin W, Keane WF: Lipids and the kidney. Hypertension 15:443–450, 1990 | PubMed | ISI | ChemPort |
  34. Rabelink AJ, Hene RJ, Erkelens DW, Joles JA, Koomans HA: Partial remission of nephrotic syndrome in patients on long-term simvastatin. Lancet 335:1045–1046, 1990 | Article | PubMed | ISI | ChemPort |
  35. Utsunomiya K, Kurata H, Yoshizawa N, Nomura K, Sasaki T, Ikeda Y: The preventive effect of pravastatin, HMG-CoA reductase inhibitor, on diabetic nephropathy. (abstract) Diabetologia 32:550A, 1989

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