Angiotensin as a Renal Growth Promoting Factor

  • Gunter Wolf
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 377)

Summary

The kidney has been traditionally considered to be one the pivotal organs involved in the systemic actions of the renin-angiotensin system (RAS) with renin produced in the juxtaglomerular apparatus and angiotensin II (ANG II) as a key player in the regulation of glomerular hemodynamics. However, many studies in the last decade, facilitated by a throughout molecular characterization of all elements of the RAS, have provided convincing evidence that the kidney exhibits a local RAS which may independently function from the systemic actions of the endocrine RAS. Moereover, even local distinct cell populations along the nephron possess all components of a functioning RAS. For example, proximal tubular cells express mRNA and protein for angiotensinogen, renin, and angiotensin converting enzyme (ACE). They bear different types of ANG II receptors with the appropriate signal transduction systems, and these cells also exhibit surface proteases like angiotensinase A which are required for the inactivation of ANG II. Moreover, recent studies in the isolated perfused kidney have clearly shown that proximal tubular cells produce considerable amounts of ANG II and these concentrations exceed approximately hundred times the systemic concentration of the peptide. Besides the well-known regulation of glomerular hemodynamics by contraction of the efferent glomerular arteriole and mesangium cells, ANG II influences transport and acidification processes in proximal and distal tubules. In addition, the octapeptide stimulates metabolic pathways like tubular gluconeogenesis and ammoniagenesis. Accumulating data over the last years derived from in vivo and in vitro studies have demonstrated that ANG II is also a growth factor for renal cells. For example, cell culture experiments have shown that the octapeptide stimulates proliferation or hypertrophy of mesangial cells. In contrast, proliferation of cultured proximal tubular cells is inhibited by ANG II and cellular hypertrophy of these cells is induced. Many studies have provided evidence that early mesangial proliferation/hypertrophy and tubular hypertrophy is a predecessor of the subsequent development of glomerulosclerosis and interstitial fibrosis, situations with irreversible morphological changes of the kidney’s architecture leading finally to end-stage renal disease. Therefore, the identification of ANG II as a renal growth factor and a better understanding of its local intrarenal synthesis and growth stimulating effects on different cell types along the nephron may help to develop rational therapeutic interventions to prevent the progression of renal disease.

Keywords

Atrial Natriuretic Peptide Mesangial Cell Proximal Tubular Cell Unilateral Ureteral Obstruction Cellular Hypertrophy 
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.

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References

  1. 1.
    Anderson PW, Do YS, Hsueh WA: Angiotensin II causes mesangial cell hypertrophy. Hypertension 1993; 21: 29–35.PubMedCrossRefGoogle Scholar
  2. 2.
    Anderson S, Rennke HG, Brenner BM. Therapeutic advantage of converting enzyme inhibitors in arresting progressive renal disease associated with systemic hypertension in the rat. J Clin Invest 1986; 77: 1993–2000.PubMedCrossRefGoogle Scholar
  3. 3.
    Blantz RC, Gabbai FB, Tucker BJ, Yamamoto T, Wilson CB. Role of mesangial cell in glomerular response to volume and angiotensin II. Am J Physiol 1993; 264: F158–F165.PubMedGoogle Scholar
  4. 4.
    Bloch RDE, Zikos D, Fisher KA, Schleicher L, Oyama M, Cheng JC, Skopicki HA, Sukowski EJ, Cragoe EJ, Peterson DR. Activation of proximal tubular Na+-H+ exchange by angiotensin II. Am Physiol 1992; 263: F135–F143.Google Scholar
  5. 5.
    Campbell DJ. Circulating and tissue angiotensin systems. J Clin Invest 1987; 79: 1–6.PubMedCrossRefGoogle Scholar
  6. 6.
    Chansel D, Dussaule JC, Ardaillou N, Ardaillou R. Identification and regulation of renin in human cultured mesangial cells. Am J Physiol 1987; 252: F32–F38.PubMedGoogle Scholar
  7. 7.
    Chobanian MC, Julin CM. Angiotensin II stimulates ammoniagenesis in canine renal proximal tubule segments. Am J Physiol 1991; 260: F19–F26.PubMedGoogle Scholar
  8. 8.
    Correa-Rotter R, Perez-Gastillo A, Chmielewski D, Rosenberg ME. Relationship between renin, angiotensinogen and histone H2b messenger ribonucleic acid in the maturing rat kidney. Nephron 1992; 62: 322–327.PubMedCrossRefGoogle Scholar
  9. 9.
    Diamond JR, Anderson S. Irreversible tubulointerstitial damage associated with chronic aminonucleosid nephrosis. Amelioration by angiotensin I converting enzyme inhibition. Am J Pathol 1990; 137: 1323–1332.Google Scholar
  10. 10.
    Douglas JG, Romero M, Hopfer U. Signaling mechanisms coupled to the angiotensin receptor of proximal tubular epithelium. Kidney Int 1990; 38 (Suppl.3330): S43–S47.Google Scholar
  11. 11.
    Dzau VJ, Burt DW, Pratt RE. Molecular biology of the renin-angiotensin system. Am J Physiol 1988; 255: F563–F573.PubMedGoogle Scholar
  12. 12.
    Edwards RM, Aiyar N. Angiotensin II receptor subtypes in the kidney. J Am Soc Nephrol 1993; 3: 1643–1652.PubMedGoogle Scholar
  13. 13.
    Faraggiana T, Venkataseshan VS, Inagami T, Churg J. Immunohistochemical localization of renin in end-stage kidneys. Am J Kidney Dis 1988; 12: 194–199.PubMedGoogle Scholar
  14. 14.
    Fine L. The biology of renal hypertrophy. Kidney Int 1986; 29: 619–634.PubMedCrossRefGoogle Scholar
  15. 15.
    Force T, Kyriakis JM, Avruch J, Bonventre JV. Endothelin, vasopressin, and angiotensin II enhance tyrosine phosphorylation by protein kinase C-dependent and-independent pathways in glomerular mesangial cells. J Biol Chem 1991; 266: 6650–6656.PubMedGoogle Scholar
  16. 16.
    Friberg P, Sundelin B, Bohman SO, Bobik A, Nilsson H, Wickman A, Gustafsson H, Petersen J, Adams MA. Renin-angiotensin system in neonatal rats: induction of a renal abnormality in response to ACE inhibition or angiotensin II antagonims. Kidney Int 1994; 45: 485–492.PubMedCrossRefGoogle Scholar
  17. 17.
    Fröhlich ED. Angiotensin converting enzyme inhibitors. Present and future. Hypertension 1989; 13 (Suppl. 1): 1125–1130.Google Scholar
  18. 18.
    Geibel J, Giebisch G, Boron WF. Angiotensin II stimulates both Na+-H+ exchange and Na+/HCO 3 cotransport in the rabbit proximal tubule. Proc Natl Acad Sci USA 1990; 87: 7919–7920.CrossRefGoogle Scholar
  19. 19.
    Giachelli CM, Pichler R, Lombardi D, Denhardt DT, Alpers CE, Schwartz SM, Johnson RJ. Osteopontin expression in angiotensin II-induced tubulointerstitial nephritis. Kidney Int 1994; 45: 515–524.PubMedCrossRefGoogle Scholar
  20. 20.
    Gomez RA, Chevalier RL, Carey RM, Peach MJ. Molecular biology of the renal renin-angiotensin system. Kidney Int 1990; 38 (Suppl.30): S18–S23.Google Scholar
  21. 21.
    Goligorsky MS, Osborne D, Howard T, Hruska KA, Karl IE. Hormonal regulation of gluconeogenesis in cultured proximal tubular cells: role of cytosolic calcium. Am J Physiol 1987; 253: F802–F809.PubMedGoogle Scholar
  22. 22.
    Harris PJ. Regulation of proximal tubule function by angiotensin. Clin Exp Pharmacol Physiol 1992; 19: 213–222.PubMedCrossRefGoogle Scholar
  23. 23.
    Harris RC. Regulation of S6 kinase activity in renal proximal tubule. Am J Physiol 1992; 263: F127–F1344.PubMedGoogle Scholar
  24. 24.
    Harris RC, Akai Y, Yasuda T, Homma T. The role of physical forces in alterations of mesangial cell function. Kidney Int 1994; 45 (Suppl.45): S17–S21.Google Scholar
  25. 25.
    Horster M, Sone M. Peptide-dependent regulation of epithelial nephron functions. Klin Wochenschr 1989; 67: 852–857.PubMedCrossRefGoogle Scholar
  26. 26.
    Hunt MK, Ramos SP, Geary KM, Norling LL, Peach MJ, Gomez RA, Carey RM. Colocalization and release of angiotensin and renin in renal cortical cells. Am J Physiol 1992; 263: F363–F373.PubMedGoogle Scholar
  27. 27.
    Ichikawa I, Harris RC. Angiotensin actions in the kidney: renewed insight into the old hormone. Kidney Int 1991; 440: 583–596.CrossRefGoogle Scholar
  28. 28.
    Ikemoto F, Song GB, Tominaga M, Kanayama Y, Yamamoto K. Angiotensin-converting enzyme in the rat kidney. Activity, distribution, and response to angiotensin-converting enzyme inhibitors. Nephron 1990;55(Suppl. l):3–9.PubMedCrossRefGoogle Scholar
  29. 29.
    Ikoma M, Kawamura T, Kakinuma Y, Fogo A, Ichikawa I. Cause of variable therapeutic efficiency of angiotensin converting inhibitor on glomerular lesions. Kidney Int 1991; 40: 195–202.PubMedCrossRefGoogle Scholar
  30. 30.
    Inagami T, Mizuno K, Kawamura M, Okamura T, Clemens DL, Higashimori K. Localization of components of the renin-angiotensin system within the kidney and sustained release of angiotensins from isolated and perfused kidney. Tohoku J Exp Med 1992; 166: 17–26.PubMedCrossRefGoogle Scholar
  31. 31.
    Ingelfinger JR, Dzau VJ. Molecular biology of renal injury: emphasis on the role of the renin-angiotensin system. J Am Soc Nephrol 1991; 2: S9–S20.PubMedGoogle Scholar
  32. 32.
    Johnson RJ, Alpers CE, Yoshimura A, Lombardi D, Pritzl P, Floege J, Schwartz SM. Renal injury from angiotensin II-mediated hypertension. Hypertension 1992; 19: 464–474.PubMedCrossRefGoogle Scholar
  33. 33.
    Johnston CL, Fabris B, Jandeleit K. Intrarenal renin-angiotensin system in renal physiology and patho-physiology. Kidney Int 1993; 44 (Suppl. 2): S59–S63.Google Scholar
  34. 34.
    Kaneto H, Morrissey JJ, McCrcaken R, Reyers A, Klahr S. Enalapril reduces collagen type IV synthesis and expansion of the interstitium in the obstructed rat kidney. Kidney Int 1994; 45: 1637–1647.PubMedCrossRefGoogle Scholar
  35. 35.
    Kastner PR, Hall JE, Guyton AC. Control of glomerular filtration rate: role of intrarenally formed angiotensin II. Am J Physiol 1984; 246: F897–F906.PubMedGoogle Scholar
  36. 36.
    Katz AM. Angiotensin II: hemodynamic regulator or growth factor? J Mol Cell Cardiol 1990; 22: 739–747.PubMedCrossRefGoogle Scholar
  37. 37.
    Keane WF, Raij L. Relationship among altered glomerular barrier permselectivity, angiotensin II, and mesangial uptake of macromolecules. Lab Invest 1985; 52: 599–604.PubMedGoogle Scholar
  38. 38.
    Kunert-Radek J, Stepien H, Komorowski J, Pawlikowski M. Stimulatory effect of angiotensin II on the proliferation of mouse spleen lymphocytes in vitro is mediated via both types of angiotensin II receptors. Biochem Biophys Res Commun 1994; 198: 1034–1039.PubMedCrossRefGoogle Scholar
  39. 39.
    Klahr S, Schreiner G, Ichikawa I. The progression of renal disease. N Engl J Med 1988; 318: 1657–1666.PubMedCrossRefGoogle Scholar
  40. 40.
    Lafferty HM, Brenner BM. Are glomerular hypertension and hypertrophy independent risk factors for the progression of renal disease? Sem Nephrol 1990; 10: 294–304.Google Scholar
  41. 41.
    Liu FY, Cogan MG. Angiotensin II stimulates early proximal bicarbonate absorption in the rat by decreasing cyclic adenosine monophosphate. J Clin Invest 1989; 84: 83–91.PubMedCrossRefGoogle Scholar
  42. 42.
    Liu FY, Cogan MG. Angiotensin II: a potent regulator of acidification in the rat early proximal convoluted tubule. J Clin Invest 1987; 80: 272–275.PubMedCrossRefGoogle Scholar
  43. 43.
    Madhun ZT, Goldthwait DA, McKay D, Hopfer U, Douglas JG. An epoxygenase metabolite of archidonic acid mediates angiotensin II-induced rises in cytosolic calcium in rabbit proximal tubule epithelial cells. J Clin Invest 1991; 88: 456–461.PubMedCrossRefGoogle Scholar
  44. 44.
    Michel B, Grima M, Coquard C, Welsch C, Barthelmebs M, Imbs JL. Effects of dietary protein and uninephrectomy on renal angiotensin converting enzyme activity in the rat. Kidney Int 1994; 45: 1587–1592.PubMedCrossRefGoogle Scholar
  45. 45.
    Millan MA, Carvallo P, Izumi SI, Zemel S, Catt KJ, Aguilera G. Novel sites of expression of functional angiotensin II receptors in the late gestation fetus. Science 1989; 244: 1340–1342.PubMedCrossRefGoogle Scholar
  46. 46.
    Miskell C A, Simpson DP. Hyperplasia precedes increased glomerular filtration rate in rat remnant kidney. Kidney Int 1990; 37: 758–766.PubMedCrossRefGoogle Scholar
  47. 47.
    Moe OW, Ujiie K, Star RA, Miller RT, Widell J, Alpern RJ, Henrich WL. Renin expression in renal proximal tubule. J Clin Invest 1993; 91: 774–779.PubMedCrossRefGoogle Scholar
  48. 48.
    Morduchowicz GA, Sheik-Hamad D, Dwyer BE, Stern N, Jo OD, Yanagawa N. Angiotensin II directly increases rabbit renal brush-border membrane sodium transport: presence of local signal transduction system. J Membrane Biol 1991; 122: 43–53.CrossRefGoogle Scholar
  49. 49.
    Nath KA. Tubulointerstitial changes as a major determinant in the progression of renal damage. Am J Kidney Dis 1992; 20: 1–17.PubMedGoogle Scholar
  50. 50.
    Navar LG, Rosivall L. Contribution of the renin-angiotensin system to the control of intrarenal hemody-namics. Kidney Int 1984; 25: 857–868.PubMedCrossRefGoogle Scholar
  51. 51.
    Neuringer JR, Brenner BM. Hemodynamic theory of progressive renal disease: a 10-year update in brief review. Am J Kidney Dis 1993; 22: 98–104.PubMedGoogle Scholar
  52. 52.
    Neuwirth R, Satriano JA, DeCandido S, Clay K, Schlondorff D. Angiotensin II causes formation of platelet activating factor in cultured rat mesangial cells. Circ Res 1989; 644: 1224–1229.CrossRefGoogle Scholar
  53. 53.
    Norman J, Badie-Dezfooly B, Nord EP, Kurtz I, Schlosser J, Chaudhari A, Fine LG. EGF-induced mitogenesis in proximal tubular cells: potentiation by angiotensin II. Am J Physiol 1987; 253: F299–F309.PubMedGoogle Scholar
  54. 54.
    Norman JT. The role of angiotensin II in renal growth. Renal Physiol Biochem 1991; 144: 175–185.Google Scholar
  55. 55.
    Ong ACM, Fine LG: Loss of glomerular function and tubulointerstitial fibrosis: cause or effect? Kidney Int 1994; 45: 345–351.PubMedCrossRefGoogle Scholar
  56. 56.
    Pelayo JC, Quan AH, Shanley PF. Angiotensin II control of the renal microcirculation in rats with reduced renal mass. Am J Physiol 1990; 258: F414–F422.PubMedGoogle Scholar
  57. 57.
    Pimentel JL, Wang S, Martinez-Maldonado M. Regulation of the renal angiotensin II receptor gene in acute unilateral ureteral obstruction. Kidney Int 1994; 45: 1614–1621.PubMedCrossRefGoogle Scholar
  58. 58.
    Radeke HH, Resch K. The inflammatory function of renal glomerular mesangial cells and their interaction with the cellular immune system. Clin Invest 1992; 70: 825–842.CrossRefGoogle Scholar
  59. 59.
    Ray PE, Aguilera G, Kopp JB, Horikoshi S, Klotman PE. Angiotensin II receptor-mediated proliferation of cultured human fetal mesangial cells. Kidney Int 1991; 440: 764–771.CrossRefGoogle Scholar
  60. 60.
    Ray PE, Bruggeman LA, Horikoshi S, Aguilera G, Klotman PE. Angiotensin II stimulates human fetal mesangial cell proliferation and fibronectin biosynthesis by binding to AT1 receptors. Kidney Int 1994; 45: 177–184.PubMedCrossRefGoogle Scholar
  61. 61.
    Rosenberg, ME, Hostetter TH. Effect of angiotensin II and norepinephrine on early growth response genes in the rat kidney. Kidney Int 1993; 43: 601–609.PubMedCrossRefGoogle Scholar
  62. 62.
    Rosenberg ME, Correa-Rotter R, Inagami T, Kren SM, Hostetter TH. Glomerular renin synthesis and storage in the remnant kidney in the rat. Kidney Int 1991; 40: 677–683.PubMedCrossRefGoogle Scholar
  63. 63.
    Scherberich JE, Wolf G, Albers C, Nowack A, Stuckhardt C, Schoeppe W. Glomerular and tubular membrane antigens reflecting cellular adaptation in human renal failure. kidney Int 1989; 36 (Suppl. 27): S38–S51.Google Scholar
  64. 64.
    Schulze-Lohoff E, Köhler M, Fees H, Reindl N, Sterzel RB. Divergent effects of arginine vasopressin and angiotensin II on proliferation and expression of the immediate early genes c-fos, c-jun and Egr-1 in cultured rat glomerular mesangial cells. J Hyperten 1993; 11: 127–134.CrossRefGoogle Scholar
  65. 65.
    Schuster VL, Kokko JP, Jacobson HR. Angiotensin II directly stimulates sodium transport in rabbit proximal convoluted tubules. J Clin Invest 1984; 73: 507–515.PubMedCrossRefGoogle Scholar
  66. 66.
    Seikaly MG, Arant BS, Seney FD. Endogenous angiotensin concentrations in specific intrarenal fluid compartments of the rat. J Clin Invest 1990; 86: 1352–1357.PubMedCrossRefGoogle Scholar
  67. 67.
    Sigmund CD, Gross KW. Structure, expression, and regulation of the murine renin genes. Hypertension 1991; 18: 446–457.PubMedCrossRefGoogle Scholar
  68. 68.
    Singhal PC, Franki N, Gibbons N, Hays RM. Effects of angiotensin II and arginine vasopressin on F-actin content of cultured mesangial cells. J Am Soc Nephrol 1992; 3: 80–87.PubMedGoogle Scholar
  69. 69.
    Stein H, Feddergreen W, Kashgarian M, Sterzel RB. Role of angiotensin II-induced renal functional changes in mesangial deposition of exogenous ferritin in rats. Lab Invest 1983; 49: 270–280.PubMedGoogle Scholar
  70. 70.
    Takeda K, Meyer-Lehnert H, Kim JK, Schrier RW. Effect of angiotensin II on Ca2+ kinetics and contraction in cultured rat glomerular mesangial cells. Am J Physiol 1988; 254: F254–F266.PubMedGoogle Scholar
  71. 71.
    Tanaka R, Kon V, Yoshioka T, Ichikawa I, Fogo A. Angiotensin converting enzyme inhibitor modulates glomerular function and structure by distinct mechanisms. Kidney Int 1994; 45: 537–5443.PubMedCrossRefGoogle Scholar
  72. 72.
    Taugner R, Hachenthal E, Inagami T, Nobiling R, Poulsen K. Vascular and tubular renin in the kidneys of mice. Histochemistry 1982; 75: 473–484.PubMedCrossRefGoogle Scholar
  73. 73.
    Taugner R, Hackenthal E, Helmchen U, Ganten D, Kugler P, Marin-Grez M, Nobiling R, Unger T, Lockwald I, Keilbach R. The intrarenal renin-angiotensin-system. An immunocytochemical study on the localization of renin, angiotensinogen converting enzyme and the angiotensins in the kidney of mouse and rat. Klin Wochenschr 1982; 60: 1218–1222.Google Scholar
  74. 74.
    Terada Y, Tomita K, Nonoguchi H, Marumo F. PCR localization of angiotensin II receptor and angiotensinogen mRNAs in rat kidney. Kidney Int 1993; 43: 1251–1259.PubMedCrossRefGoogle Scholar
  75. 75.
    Torres VE, Donovan KA, Scicli G, Holley KE, Thibodeau SN; Carretero OA, Inagami T, McAteer JA; Johnson CM. Synthesis of renin by tubulocystic epithelium in autosomal-dominant polycystic kidney disease. Kidney Int 1992; 42: 364–373.PubMedCrossRefGoogle Scholar
  76. 76.
    Tufro-McReddie A, Harrison JK, Everett AD, Gomez RA. Ontogeny of type 1 angiotensin II receptor gene expression in the rat. J Clin Invest 1993; 91: 530–537.PubMedCrossRefGoogle Scholar
  77. 77.
    Uemasu J, Fujiwara M, Munemura C, Kawasaki H. Long-term effects of enalapril in rat with experimental chronic tubulo-interstitial nephropathy. Am J Nephrol 1993; 13: 35–42.PubMedCrossRefGoogle Scholar
  78. 78.
    Wight JP, Bassett AH, Le Carpentier JE, El Nahas AM. Effect of treatment with enalapril, verapamil and indomethacin on compensatory renal growth in the rat. Nephrol, Dial, Transplant 1990; 5: 777–780.CrossRefGoogle Scholar
  79. 79.
    Wolf G, Thaiss F, Scherberich JE, Schoeppe W, Stahl RAK: Glomerular angiotensinase A in the rat: increase of enzyme activity following renal ablation. Kidney Int 1990; 38: 862–868.PubMedCrossRefGoogle Scholar
  80. 80.
    Wolf G, Neilson EG. Angiotensin II induces cellular hypertrophy in cultured murine proximal tubular cells. Am J Physiol 1990; 259: F768–F777.PubMedGoogle Scholar
  81. 81.
    Wolf G, Neilson EG. Molecular mechanisms of tubulointerstitial hypertrophy and hyperplasia. Kidney Int 1991; 39: 401–420.PubMedCrossRefGoogle Scholar
  82. 82.
    Wolf G, Killen PD, Neilson EG. Intracellular signaling of transcription and secretion of type IV collagen after angiotensin II-induced cellular hypertrophy in cultured proximal tubular cells. Cell Reg 1991; 2: 219–227.Google Scholar
  83. 83.
    Wolf G, Kuncio GS, Sun MJ, Neilson EG. Expression of homeobox genes in a proximal tubular cell line derived from adult mice. Kidney Int 1991; 39: 1027–1033.PubMedCrossRefGoogle Scholar
  84. 84.
    Wolf G, Neilson EG, Goldfarb S, Ziyadeh FN. The influence of glucose concentration on angiotensin II-induced hypertrophy of proximal tubular cells in culture. Biochem Biophys Res Commun 1991; 176: 902–909.PubMedCrossRefGoogle Scholar
  85. 85.
    Wolf G, Haberstroh U, Neilson EG. Angiotensin II stimulates the proliferation and biosynthesis of type I collagen in cultured murine mesangial cells. Am J Pathol 1992; 140: 95–107.PubMedGoogle Scholar
  86. 86.
    Wolf G, Thaiss F, Schoeppe W, Stahl RAK. Angiotensin II-induced proliferation of cultured murine mesangial cells: inhibitory role of atrial natriuretic peptide. J Am Soc Nephrol 1992; 3: 1270–1278.PubMedGoogle Scholar
  87. 87.
    Wolf G, Neilson EG. Effects of angiotensin II on proximal tubular cells stbaly transfected with the c-mas oncogene. Am J Physiol 1992; 263: F931–F938.PubMedGoogle Scholar
  88. 88.
    Wolf G, Neilson EG. Angiotensin II as a renal growth factor. J Am Soc Nephrol 1993; 3: 1531–1540.PubMedGoogle Scholar
  89. 89.
    Wolf G, Neilson EG. Angiotensin II as a hypertrophogenic cytokine for proximal tubular cells. Kidney Int 1993; 43 (Suppl.39): S100–S107.Google Scholar
  90. 90.
    Wolf G, Zahner G, Mondorf U, Schoeppe W, Stahl RAK. Angiotensin II stimulates cellular hypertrophy of LLC-PK, cells through the AT, receptor. Nephrol, Dial, Transplant 1993; 8: 128–133.Google Scholar
  91. 91.
    Wolf G. Vasoactive substances as regulators of renal growth. Exp Nephrol 1993; 1: 141–151.PubMedGoogle Scholar
  92. 92.
    Wolf G, Mueller E, Stahl RAK, Ziyadeh FN. Angiotensin II-induced hypertrophy of cultured murine proximal tubular cells is mediated by endogenous transforming growth factor-β. J Clin Invest 1993; 92: 1366–1372.PubMedCrossRefGoogle Scholar
  93. 93.
    Wolf G. Regulation of renal tubular cell growth: effects of angiotensin II. Exp Nephrol 1994; 2: 107–114.PubMedGoogle Scholar
  94. 94.
    Wolf G, Neilson EG. Angiotensin II as a renal cytokine. News Physiol Scie 1994; 9: 40–42.Google Scholar
  95. 95.
    Wolf G, Mueller E, Bergmann L, Thaiss F, Stahl RAK, Ziyadeh FN. Angiotensin (A II) induces mitogenesis in a murine tubular cell line isolated from thick ascending lim (TAL; abstract). J Am Soc Nephrol 1993; 4: 449.Google Scholar
  96. 96.
    Wolthuis A, Boes A, Rodemann HP, Grond J. Vasoactive agents affect growth and protein synthesis of cultured rat mesangial cells. Kidney Int 1992; 41: 1244–131.CrossRefGoogle Scholar
  97. 97.
    Woodcock EA, Johnston CL. Inhibition of adenylate cyclase by angiotensin II in rat renal cortex. Endocrinology 1982; 111: 1687–1691.PubMedCrossRefGoogle Scholar
  98. 98.
    Yanagawa N, Capparelli W, Jo OD, Friedal A, Barrett JD, Eggena P. Production of angiotensinogen and renin-like activity by rabbit proximal tubular cells in culture. Kidney Int 1991; 39: 938–941.PubMedCrossRefGoogle Scholar
  99. 99.
    Yoshida Y, Fogo A, Ichikawa I. Glomerular hemodynamic changes vs. hypertrophy in experimental glomerular sclerosis. Kidney Int 1989; 35: 654–660.CrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 1995

Authors and Affiliations

  • Gunter Wolf
    • 1
  1. 1.Department of Medicine, Division of Nephrology and OsteologyUniversity of Hamburg, University Hospital EppendorfHamburgGermany

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