The Renin-Angiotensin System and the Aging Process

  • Léon Ferder
  • Manuel Martinez-Maldonado


Seminal Plasma Mitochondrial Number Kidney Mitochondrion Mitochondrial Hydrogen Peroxide Calcium Channel Blocker Amlodipine 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. Harman, D. The aging process. Proc. Natl. Acad. Sci. USA 1981; 78(11):7124–7128.Google Scholar
  2. Shock, N.W. Physiologic aspects of aging. J. Am. Diet. Assoc. 1970; 56(6):491–496.PubMedGoogle Scholar
  3. Hayflick, L. Recent advances in the cell biology of aging. Mech, Ageing Dev. 1980; 14(1–2):59–79.Google Scholar
  4. Miquel, J., Economos, A.C., Fleming, J., Johnson, J.E., Jr. Mitochondrial role in cell aging. Exp. Gerontol. 1980; 15(6):575–591.PubMedGoogle Scholar
  5. Thomas, D.D., Liu, X., Kantrow, SP., Lancaster, J.R., Jr. The biological lifetime of nitric oxide: Implications for the perivascular dynamics of NO and O2. Proc. Natl. Acad. Sci. USA 2001; 98(1):355–360.Google Scholar
  6. Brookes, P.S., Salinas, E.P., Darley-Usmar, K., et al. Concentration-dependent effects of nitric oxide on mitochondrial permeability transition and cytochrome C release. J. Biol. Chem. 2000; 275(27):20474–20479.PubMedGoogle Scholar
  7. Brookes, P., Darley-Usmar, V.M. Hypothesis: The mitochondrial NO(*) signaling pathway, and the transduction of nitrosative to oxidative cell signals: An alternative function for cytochrome C oxidase. Free Radic. Biol. Med. 2002; 32(4):370–374.PubMedGoogle Scholar
  8. Harman, D. Free radical theory of aging: Consequence of mitochondrial aging. Age 1983; 6:86–94.Google Scholar
  9. Pollack, M., Leeuwenburgh, C. Apoptosis and aging: Role of the mitochondria. J. Gerontol. A Biol. Sci. Med. Sci. 2001; 56(11):B475–482.PubMedGoogle Scholar
  10. Ferder, L., Inserra, F., Romano, L., Ercole, L., Pszenny, V. Effects of angiotensin-converting enzyme inhibition on mitochondrial number in the aging mouse. Am. J. Physiol. 1993; 265(1 Pt 1):C15–18.PubMedGoogle Scholar
  11. de Cavanagh, E.M., Fraga, C.G., Ferder, L., Inserra, F. Enalapril and captopril enhance antioxidant defenses in mouse tissues. Am. J. Physiol. 1997; 272(2 Pt 2):R514–518.PubMedGoogle Scholar
  12. de Cavanagh, E.M., Inserra, F., Ferder, L., Fraga, C.G. Enalapril and captopril enhance glutathione-dependent antioxidant defenses in mouse tissues. Am. J. Physiol. Regul. Integr. Comp. Physiol. 2000; 278(3):R572–577.PubMedGoogle Scholar
  13. Ferder, L., Romano, L.A., Ercole, L.B., Stella, I., Inserra, F. Biomolecular changes in the aging myocardium: The effect of enalapril. Am. J. Hypertens. 1998; 11(11 Pt 1):1297–1304.PubMedGoogle Scholar
  14. Assayag, P., Charlemagne, D., de Leiris, J., et al. Senescent heart compared with pressure overload-induced hypertrophy. Hypertension 1997; 29(1 Pt 1):15–21.PubMedGoogle Scholar
  15. Benetos, A., Laurent, S., Hoeks, A.P., Boutouyrie, P.H., Safar, M.E. Arterial alterations with aging and high blood pressure. A noninvasive study of carotid and femoral arteries. Arterioscler. Thromb. 1993; 13(1):90–97.PubMedGoogle Scholar
  16. Michel, J.B., Azizi, M., Salzmann, J.L., Levy, B., Menard, J. Effect of vasodilatators on the structure of the aorta in normotensive ageing rats. J. Hypertens. Suppl. 1987; 5(5):S165–168.PubMedGoogle Scholar
  17. Collister, J.P., Hornfeldt, B.J., Osborn, J.W. Hypotensive response to losartan in normal rats. Role of Ang II and the area postrema. Hypertension 1996; 27(3 Pt 2):598–606.PubMedGoogle Scholar
  18. Inserra, F., Romano, L., Ercole, L., de Cavanagh, E.M., Ferder, L. Cardiovascular changes by long-term inhibition of the renin-angiotensin system in aging. Hypertension 1995; 25(3):437–442.PubMedGoogle Scholar
  19. Keeley, F.W., Elmoselhi, A., Leenen, F.H. Enalapril suppresses normal accumulation of elastin and collagen in cardiovascular tissues of growing rats. Am. J. Physiol. 1992; 262(4 Pt 2):H1013–1021.PubMedGoogle Scholar
  20. Bunnemann, B., Fuxe, K., Ganten, D. The renin-angiotensin system in the brain: An update. Regul. Pept. 1993; 46(3):487–509.PubMedGoogle Scholar
  21. Wright, J.W., Harding, J.W. Brain angiotensin receptor subtypes in the control of physiological and behavioral responses. Neurosci. Biobehav. Rev. 1994; 18(1):21–53.PubMedGoogle Scholar
  22. Phillips, M.I. Functions of angiotensin in the central nervous system. Ann. Rev. Physiol. 1987; 49:413–435.Google Scholar
  23. Unger, T., Chung, O., Csikos, T., et al. Angiotensin receptors. J. Hypertens. Suppl. 1996; 14(5):S95–103.PubMedGoogle Scholar
  24. Hirawa, N., Uehara, Y., Kawabata, Y., et al. Long-term inhibition of renin-angiotensin system sustains memory function in aged Dahl rats. Hypertension 1999; 34(3):496–502.PubMedGoogle Scholar
  25. Stemmelin, J., Cassel, J.C., Will, B., Kelche, C. Sensitivity to cholinergic drug treatments of aged rats with variable degrees of spatial memory impairment. Behav. Brain Res. 1999; 98(1):53–66.PubMedGoogle Scholar
  26. Colombo, P.J., Gallagher, M. Individual differences in spatial memory and striatal ChAT activity among young and aged rats. Neurobiol. Learn. Mem. 1998; 70(3):314–327.PubMedGoogle Scholar
  27. Sugaya, K., Greene, R., Personett, D., et al. Septo-hippocampal cholinergic and neurotrophin markers in age-induced cognitive decline. Neurobiol. Aging 1998; 19(4):351–361.PubMedGoogle Scholar
  28. Yamada, K., Noda, Y., Komori, Y., Sugihara, H., Hasegawa, T., Nabeshima, T. Reduction in the number of NADPH-diaphorase-positive cells in the cerebral cortex and striatum in aged rats. Neurosci. Res. 1996; 24(4):393–402.PubMedGoogle Scholar
  29. Noda, Y., Yamada, K., Nabeshima, T. Role of nitric oxide in the effect of aging on spatial memory in rats. Behav. Brain Res. 1997; 83(1–2):153–158.PubMedGoogle Scholar
  30. Basso, N., Altamirano, S., Paglia, N., Ferder, L., Inserra, F., Lores Arnaiz, M. Long-term inhibition of the RAS improves spatial working memory in the rat. J. Hypertens. 2000; 18(Suppl 4):S77.Google Scholar
  31. Basso, N., Altamirano, S., Terragno, N., Ferder, L., Inserra, F., Lores Arnaiz, M. Inhibition of the renin-angiotensin system improves spatial working memory in the senile normal rat. J. Hypertens. 2002; 20(Suppl 4):S134.Google Scholar
  32. Michel, J.B., Salzmann, J.L., Cerol, M.L., et al. Myocardial effect of converting enzyme inhibition in hypertensive and normotensive rats. Am. J. Med. 1988; 84(3A):12–21.PubMedGoogle Scholar
  33. Gaballa, M.A., Jacob, C.T., Raya, T.E., Liu, J., Simon, B., Goldman, S. Large artery remodeling during aging: Biaxial passive and active stiffness. Hypertension 1998; 32(3):437–443.PubMedGoogle Scholar
  34. Kung, C.F., Luscher, T.F. Different mechanisms of endothelial dysfunction with aging and hypertension in rat aorta. Hypertension 1995; 25(2):194–200.PubMedGoogle Scholar
  35. Heagerty, A.M. Functional and structural effects of ACE inhibitors on the cardiovascular system. Cardiology 1991; 79(Suppl 1):3–9.PubMedGoogle Scholar
  36. Park, J.B., Intengan, H.D., Schiffrin, E.L. Reduction of resistance artery stiffness by treatment with the AT(1)-receptor antagonist losartan in essential hypertension. J. Renin Angiotensin Aldosterone Syst. 2000; 1(1):40–45.PubMedGoogle Scholar
  37. Gonzalez Bosc, L., Kurnjek, M.L., Muller, A., Basso, N. Effect of chronic angiotensin II inhibition on the cardiovascular system of the normal rat. Am. J. Hypertens. 2000; 13(12):1301–1307.PubMedGoogle Scholar
  38. Gonzalez Bosc, L.V., Kurnjek, M.L., Muller, A., Terragno, N.A., Basso, N. Effect of chronic angiotensin II inhibition on the nitric oxide synthase in the normal rat during aging. J. Hypertens. 2001; 19(8):1403–1409.PubMedGoogle Scholar
  39. Anversa, P., Palackal, T., Sonnenblick, E.H., Olivetti, G., Meggs, L.G., Capasso, J.M. Myocyte cell loss and myocyte cellular hyperplasia in the hypertrophied aging rat heart. Circ. Res. 1990; 67(4):871–885.PubMedGoogle Scholar
  40. Chou, T.C., Yen, M.H., Li, C.Y., Ding, Y.A. Alterations of nitric oxide synthase expression with aging and hypertension in rats. Hypertension 1998; 31(2):643–648.PubMedGoogle Scholar
  41. Ferder, L.F., Inserra, F., Basso, N. Advances in our understanding of aging: Role of the renin-angiotensin system. Curr. Opin. Pharmacol. 2002; 2(2):189–194.PubMedGoogle Scholar
  42. Binder, C.J., Weiher, H., Exner, M., Kerjaschki, D. Glomerular overproduction of oxygen radicals in Mpv17 gene-inactivated mice causes podocyte foot process flattening and proteinuria: A model of steroid-resistant nephrosis sensitive to radical scavenger therapy. Am. J. Pathol. 1999; 154(4):1067–1075.PubMedGoogle Scholar
  43. Ferder, L., Inserra, F., Romano, L., Ercole, L., Pszenny, V. Decreased glomerulosclerosis in aging by angiotensin-converting enzyme inhibitors. J. Am. Soc. Nephrol. 1994; 5(4):1147–1152.PubMedGoogle Scholar
  44. Kaplan, C., Pasternack, B., Shah, H., Gallo, G. Age-related incidence of sclerotic glomeruli in human kidneys. Am. J. Pathol. 1975; 80(2):227–234.PubMedGoogle Scholar
  45. Heudes, D., Michel, O., Chevalier, J., et al. Effect of chronic ANG I-converting enzyme inhibition on aging processes. I. Kidney structure and function. Am. J. Physiol. 1994; 266(3 Pt 2):R1038–1051.PubMedGoogle Scholar
  46. Hostetter, T.H., Olson, J.L., Rennke, H.G., Venkatachalam, M.A., Brenner, B.M. Hyperfiltration in remnant nephrons: A potentially adverse response to renal ablation. Am. J. Physiol. 1981; 241(1):F85–93.PubMedGoogle Scholar
  47. Anderson, S., Meyer, T.W., Rennke, H.G., Brenner, B.M. Control of glomerular hypertension limits glomerular injury in rats with reduced renal mass. J. Clin. Invest. 1985; 76(2):612–619.PubMedGoogle Scholar
  48. Inserra, F., Romano, L.A., de Cavanagh, E.M., Ercole, L., Ferder, L.F., Gomez, R.A. Renal interstitial sclerosis in aging: Effects of enalapril and nifedipine. J. Am. Soc. Nephrol. 1996; 7(5):676–680.PubMedGoogle Scholar
  49. Kakinuma, Y., Kawamura, T., Bills, T., Yoshioka, T., Ichikawa, I., Fogo, A. Blood pressure-independent effect of angiotensin inhibition on vascular lesions of chronic renal failure. Kidney Int. 1992; 42(1):46–55.PubMedGoogle Scholar
  50. Norman, J.T. The role of angiotensin II in renal growth. Ren. Physiol. Biochem. 1991; 14(4–5):175–185.PubMedGoogle Scholar
  51. Fine, L. The biology of renal hypertrophy. Kidney Int, 1986; 29(3):619–634.PubMedGoogle Scholar
  52. Abboud, H.E. Resident glomerular cells in glomerular injury: Mesangial cells. Semin. Nephrol. 1991; 11(3):304–311.PubMedGoogle Scholar
  53. Rovin, B.H., Phan, L.T. Chemotactic factors and renal inflammation. Am. J. Kidney Dis. 1998; 31(6):1065–1084.PubMedGoogle Scholar
  54. Kato, S., Luyckx, V.A., Ots, M., et al. Renin-angiotensin blockade lowers MCP-1 expression in diabetic rats. Kidney Int. 1999; 56(3):1037–1048.PubMedGoogle Scholar
  55. Pimentel, J.L., Jr., Montero, A., Wang, S., Yosipiv, I., el-Dahr, S., Martinez-Maldonado, M. Sequential changes in renal expression of renin-angiotensin system genes in acute unilateral ureteral obstruction. Kidney Int. 1995; 48(4):1247–1253.PubMedGoogle Scholar
  56. Pimentel, J.L., Jr., Sundell, C.L., Wang, S., Kopp, J.B., Montero, A., Martinez-Maldonado, M. Role of angiotensin II in the expression and regulation of transforming growth factor-beta in obstructive nephropathy. Kidney Int. 1995; 48(4):1233–1246.PubMedGoogle Scholar
  57. Pimentel, J.L., Jr., Wang, S., Martinez-Maldonado, M. Regulation of the renal angiotensin II receptor gene in acute unilateral ureteral obstruction. Kidney Int. 1994; 45(6):1614–1621.PubMedGoogle Scholar
  58. Pimentel, J.L., Jr., Martinez-Maldonado, M., Wilcox, J.N., Wang, S., Luo, C. Regulation of renin-angiotensin system in unilateral ureteral obstruction. Kidney Int. 1993; 44(2):390–400.PubMedGoogle Scholar
  59. Manucha, W., Carrizo, L., Ruete, C., Molina, H., Valles, P. Angiotensin II type I antagonist on oxidative stress and heat shock protein 70 (HSP 70) expression in obstructive nephropathy. Cell Mol. Biol. (Noisy-le-grand) 2005; 51(6):547–555.Google Scholar
  60. Klahr, S., Morrissey, J.J. The role of growth factors, cytokines, and vasoactive compounds in obstructive nephropathy. Semin. Nephrol. 1998; 18(6):622–632.PubMedGoogle Scholar
  61. Thompson, M.M., Oyama, T.T., Kelly, F.J., Kennefick, T.M., Anderson, S. Activity and responsiveness of the renin-angiotensin system in the aging rat. Am. J. Physiol. Regul. Integr. Comp. Physiol. 2000; 279(5):R1787–1794.PubMedGoogle Scholar
  62. Shagdarsuren, E., Wellner, M., Braesen, J.H., et al. Complement activation in angiotensin II-induced organ damage. Circ. Res. 2005; 97(7):716–724.PubMedGoogle Scholar
  63. Cha, D.R., Kang, Y.S., Han, S.Y., et al. Role of aldosterone in diabetic nephropathy. Nephrology (Carlton) 2005; 10 (Suppl):S37–39.Google Scholar
  64. Inserra, F., Stella, I., Kurnjek, M., et al. Losartan and enalapril protect against age related kidney lesions in normal rats treated from 12 to 18 months of age. J. Am. Soc. Nephrol. 2001; 12:679A.Google Scholar
  65. de Cavanagh, E.M., Piotrkowski, B., Basso, N., et al. Enalapril and losartan attenuate mitochondrial dysfunction in aged rats. FASEB J. 2003; 17(9):1096–1098.PubMedGoogle Scholar
  66. Pauls, K., Metzger, R., Steger, K., Klonisch, T., Danilov, S., Franke, F.E. Isoforms of angiotensin I-converting enzyme in the development and differentiation of human testis and epididymis. Andrologia 2003; 35(1):32–43.PubMedGoogle Scholar
  67. Mededovic, S., Fraser, L.R. Mechanisms of action of angiotensin II on mammalian sperm function. Reproduction 2005; 129(2):211–218.PubMedGoogle Scholar
  68. Fraser, L.R., Adeoya-Osiguwa, S.A., Baxendale, R.W., Gibbons, R. Regulation of mammalian sperm capacitation by endogenous molecules. Front. Biosci. 2006; 11:1636–1645.PubMedGoogle Scholar
  69. Zheng, S., Li, Z., Wang, Y.X., Xiang, Z.Q. [Seminal plasma angiotensin II detection and its clinical implication.] [in Chinese] Zhonghua Nan Ke Xue 2003; 9(9):669–672.PubMedGoogle Scholar
  70. Toblli, J., Stella, I., Nestor Mazza, O., Ferder, L., Inserra, F. Protection of cavernous tissue in male spontaneously hypertensive rats. Beyond blood pressure control. Am. J. Hypertens. 2004; 17(6):516–522.PubMedGoogle Scholar
  71. Cadenas, E., Davies, K.J. Mitochondrial free radical generation, oxidative stress, and aging. Free Radic. Biol. Med. 2000; 29(3–4):222–230.PubMedGoogle Scholar
  72. Hart, R., Turturro, A. Theories of aging. Rev. Biol. Res. Aging 1983; 1:5–17.Google Scholar
  73. Murfitt, R.R., Rao Sanadi, D. Evidence for increased degeneration of mitochondria in old rats. A brief note. Mech. Ageing Dev. 1978; 8(3):197–201.PubMedGoogle Scholar
  74. Polson, C., Webster, J. Loss of mitochondrial DNA in mouse tissues with age. Age 1982; 5:5–133.Google Scholar
  75. Kukreja, R.C., Kontos, H.A., Hess, M.L. Captopril and enalapril do not scavenge the superoxide anion. Am. J. Cardiol. 1990; 65(19):24I–27I.PubMedGoogle Scholar
  76. de Cavanagh, E.M., Inserra, F., Ferder, L., Romano, L., Ercole, L., Fraga, C.G. Superoxide dismutase and glutathione peroxidase activities are increased by enalapril and captopril in mouse liver. FEBS Lett. 1995; 361(1):22–24.PubMedGoogle Scholar
  77. Jolly, S.R., Kane, W.J., Bailie, M.B., Abrams, G.D., Lucchesi, B.R. Canine myocardial reperfusion injury. Its reduction by the combined administration of superoxide dismutase and catalase. Circ. Res. 1984; 54(3):277–285.PubMedGoogle Scholar
  78. Orr, W.C., Sohal, R.S. Extension of life-span by overexpression of superoxide dismutase and catalase in Drosophila melanogaster. Science 1994; 263(5150):1128–1130.PubMedGoogle Scholar
  79. Das, N., Levine, R.L., Orr, W.C., Sohal, R.S. Selectivity of protein oxidative damage during aging in Drosophila melanogaster. Biochem. J. 2001; 360(Pt 1):209–216.Google Scholar
  80. Pueyo, M.E., Arnal, J.F., Rami, J., Michel, J.B. Angiotensin II stimulates the production of NO and peroxynitrite in endothelial cells. Am. J. Physiol. 1998; 274(1 Pt 1):C214–220.PubMedGoogle Scholar
  81. Rueckschloss, U., Quinn, M.T., Holtz, J., Morawietz, H. Dose-dependent regulation of NAD(P)H oxidase expression by angiotensin II in human endothelial cells: Protective effect of angiotensin II type 1 receptor blockade in patients with coronary artery disease. Arterioscler. Thromb. Vasc. Biol. 2002; 22(11):1845–1851.PubMedGoogle Scholar
  82. Radi, R., Cassina, A., Hodara, R., Quijano, C., Castro, L. Peroxynitrite reactions and formation in mitochondria. Free Radic. Biol. Med. 2002; 33(11):1451–1464.PubMedGoogle Scholar
  83. de Cavanagh, E.M., Toblli, J.E., Ferder, L., Piotrkowski, B., Stella, I., Inserra, F. Renal mitochondrial dysfunction in spontaneously hypertensive rats is attenuated by losartan but not by amlodipine. Am. J. Physiol. Regul. Integr. Comp. Physiol. 2006; 290(6):R1616–1625.PubMedGoogle Scholar
  84. Newaz, M.A., Nawal, N.N. Effect of gamma-tocotrienol on blood pressure, lipid peroxidation and total antioxidant status in spontaneously hypertensive rats (SHR). Clin. Exp. Hypertens. 1999; 21(8):1297–1313.PubMedGoogle Scholar
  85. Brand, M.D., Affourtit, C., Esteves, T.C., et al. Mitochondrial superoxide: Production, biological effects, and activation of uncoupling proteins. Free Radic. Biol. Med. 2004; 37(6):755–767.PubMedGoogle Scholar
  86. Rhee, S.G. Cell signaling. H2O2, a necessary evil for cell signaling. Science 2006; 312(5782):1882–1883.PubMedGoogle Scholar
  87. Cadenas, E., Poderoso, J.J., Antunes, F., Boveris, A. Analysis of the pathways of nitric oxide utilization in mitochondria. Free Radic. Res. 2000; 33(6):747–756.PubMedGoogle Scholar
  88. Negre-Salvayre, A., Hirtz, C., Carrera, G., et al. A role for uncoupling protein-2 as a regulator of mitochondrial hydrogen peroxide generation. FASEB J. 1997; 11(10):809–815.PubMedGoogle Scholar
  89. Fukunaga, Y., Itoh, H., Hosoda, K., et al. Altered gene expression of uncoupling protein-2 and -3 in stroke-prone spontaneously hypertensive rats. J. Hypertens. 2000; 18(9):1233–1238.PubMedGoogle Scholar
  90. Wallace, D.C. A mitochondrial paradigm for degenerative diseases and aging. Novartis Found. Symp. 2001; 235:247–263; discussion 63–66.PubMedGoogle Scholar
  91. Nishikawa, T., Edelstein, D., Du, X.L., et al. Normalizing mitochondrial superoxide production blocks three pathways of hyperglycaemic damage. Nature 2000; 404(6779):787–790.PubMedGoogle Scholar
  92. Hagen, T.M., Yowe, D.L., Bartholomew, J.C., et al. Mitochondrial decay in hepatocytes from old rats: Membrane potential declines, heterogeneity and oxidants increase. Proc. Natl. Acad. Sci. USA 1997; 94(7):3064–3069.PubMedGoogle Scholar
  93. Kimura, S., Zhang, G.X., Nishiyama, A., et al. Mitochondria-derived reactive oxygen species and vascular MAP kinases: Comparison of angiotensin II and diazoxide. Hypertension 2005; 45(3):438–444.PubMedGoogle Scholar
  94. Laursen, J.B., Rajagopalan, S., Galis, Z., Tarpey, M., Freeman, B.A., Harrison, D.G. Role of superoxide in angiotensin II-induced but not catecholamine-induced hypertension. Circulation 1997; 95(3):588–593.PubMedGoogle Scholar
  95. Tham, D.M., Martin-McNulty, B., Wang, Y.X., et al. Angiotensin II is associated with activation of NF-kappaB-mediated genes and downregulation of PPARs. Physiol. Genomics 2002; 11(1):21–30.PubMedGoogle Scholar
  96. Nakatani, T., Tsuboyama-Kasaoka, N., Takahashi, M., Miura, S., Ezaki, O. Mechanism for peroxisome proliferator-activated receptor-alpha activator-induced up-regulation of UCP2 mRNA in rodent hepatocytes. J. Biol. Chem. 2002; 277(11):9562–9569.PubMedGoogle Scholar
  97. Takahashi, M., Tsuboyama-Kasaoka, N., Nakatani, T., et al. Fish oil feeding alters liver gene expressions to defend against PPARalpha activation and ROS production. Am. J. Physiol. Gastrointest. Liver Physiol. 2002; 282(2):G338–348.PubMedGoogle Scholar
  98. Wilson, F.H., Hariri, A., Farhi, A., et al. A cluster of metabolic defects caused by mutation in a mitochondrial tRNA. Science 2004; 306(5699):1190–1194.PubMedGoogle Scholar
  99. Katyare, S.S., Satav, J.G. Effect of streptozotocin-induced diabetes on oxidative energy metabolism in rat kidney mitochondria. A comparative study of early and late effects. Diabetes Obes. Metab. 2005; 7(5):555–562.PubMedGoogle Scholar
  100. Raza, H., Prabu, S.K., Robin, M.A., Avadhani, N.G. Elevated mitochondrial cytochrome P450 2E1 and glutathione S-transferase A4–4 in streptozotocin-induced diabetic rats: Tissue-specific variations and roles in oxidative stress. Diabetes 2004; 53(1):185–194.PubMedGoogle Scholar
  101. Remuzzi, G., Schieppati, A., Ruggenenti, P. Clinical practice. Nephropathy in patients with type 2 diabetes. N. Engl. J. Med. 2002; 346(15):1145–1151.PubMedGoogle Scholar
  102. Lewis, E.J., Hunsicker, L.G., Bain, R.P., Rohde, R.D. The effect of angiotensin-converting-enzyme inhibition on diabetic nephropathy. The Collaborative Study Group. N. Engl. J. Med. 1993; 329(20):1456–1462.PubMedGoogle Scholar
  103. Lewis, E.J., Hunsicker, L.G., Clarke, W.R., et al. Renoprotective effect of the angiotensin-receptor antagonist irbesartan in patients with nephropathy due to type 2 diabetes. N. Engl. J. Med. 2001; 345(12):851–860.PubMedGoogle Scholar
  104. Brenner, B.M., Cooper, M.E., de Zeeuw, D., et al. Effects of losartan on renal and cardiovascular outcomes in patients with type 2 diabetes and nephropathy. N. Engl. J. Med. 2001; 345(12):861–869.PubMedGoogle Scholar
  105. Hansson, L., Lindholm, L.H., Niskanen, L., et al. Effect of angiotensin-converting-enzyme inhibition compared with conventional therapy on cardiovascular morbidity and mortality in hypertension: The Captopril Prevention Project (CAPPP) randomised trial. Lancet 1999; 353(9153):611–616.PubMedGoogle Scholar
  106. Lindholm, L.H., Ibsen, H., Dahlof, B., et al. Cardiovascular morbidity and mortality in patients with diabetes in the Losartan Intervention For Endpoint reduction in hypertension study (LIFE): A randomised trial against atenolol. Lancet 2002; 359(9311):1004–1010.PubMedGoogle Scholar
  107. Julius, S., Kjeldsen, S.E., Brunner, H., et al. VALUE trial: Long-term blood pressure trends in 13,449 patients with hypertension and high cardiovascular risk. Am. J. Hypertens. 2003; 16(7):544–548.PubMedGoogle Scholar
  108. de Cavanagh, E.M., Inserra, F., Toblli, J., Stella, I., Fraga, C.G., Ferder, L. Enalapril attenuates oxidative stress in diabetic rats. Hypertension 2001; 38(5):1130–1136.PubMedGoogle Scholar
  109. Chen, G., Lin, L.X., Zhuang, W.T., et al. [Effects of captopril on myocardial tissue energy metabolism and inflammation in rats with diabetic cardiomyopathy.] [in Chinese] Di Yi Jun Yi Da Xue Xue Bao 2004; 24(7):827–828, 831.PubMedGoogle Scholar
  110. Inserra, F., Daccordi, H., Ippolito, J.L., Romano, L., Zelechower, H., Ferder, L. Decrease of exercise-induced microalbuminuria in patients with type I diabetes by means of an angiotensin-converting enzyme inhibitor. Am. J. Kidney Dis. 1996; 27(1):26–33.PubMedGoogle Scholar
  111. Ferder, L., Daccordi, H., Martello, M., Panzalis, M., Inserra, F. Angiotensin converting enzyme inhibitors versus calcium antagonists in the treatment of diabetic hypertensive patients. Hypertension 1992; 19(2 Suppl):II237–242.PubMedGoogle Scholar
  112. Remuzzi, G., Bertani, T. Pathophysiology of progressive nephropathies. N. Engl. J. Med. 1998; 339(20):1448–1456.PubMedGoogle Scholar
  113. Randomised placebo-controlled trial of effect of ramipril on decline in glomerular filtration rate and risk of terminal renal failure in proteinuric, non-diabetic nephropathy. The GISEN Group (Gruppo Italiano di Studi Epidemiologici in Nefrologia). Lancet 1997; 349(9069):1857–1863.Google Scholar
  114. Ruggenenti, P., Perna, A., Gherardi, G., et al. Renoprotective properties of ACE-inhibition in non-diabetic nephropathies with non-nephrotic proteinuria. Lancet 1999; 354(9176):359–364.PubMedGoogle Scholar
  115. Wright, J.T., Jr., Bakris, G., Greene, T., et al. Effect of blood pressure lowering and antihypertensive drug class on progression of hypertensive kidney disease: Results from the AASK trial. JAMA 2002; 288(19):2421–2431.PubMedGoogle Scholar
  116. Kasper, S.O., Basso, N., Kurnjek, M.L., et al. Divergent regulation of circulating and intrarenal renin-angiotensin systems in response to long-term blockade. Am. J. Nephrol. 2005; 25(4):335–341.PubMedGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2008

Authors and Affiliations

  • Léon Ferder
  • Manuel Martinez-Maldonado

There are no affiliations available

Personalised recommendations