Pediatric Nephrology

, Volume 20, Issue 9, pp 1219–1229 | Cite as

Role of the renin-angiotensin system in the development of the ureteric bud and renal collecting system

Review

Abstract

Genetic, biochemical and physiological studies have demonstrated that the renin-angiotensin system (RAS) plays a fundamental role in kidney development. All of the components of the RAS are expressed in the metanephros. Mutations in the genes encoding components of the RAS in mice or pharmacological inhibition of RAS in animals or humans cause diverse congenital abnormalities of the kidney and lower urinary tract. The latter include renal vascular abnormalities, abnormal glomerulogenesis, renal papillary hypoplasia, hydronephrosis, aberrant UB budding, duplicated collecting system, and urinary concentrating defect. Thus, the actions of angiotensin (ANG) II during kidney development are pleiotropic both spatially and temporally. Whereas the role of ANG II in renovascular and glomerular development has received much attention, little is known about the potential role of ANG II and its receptors in the morphogenesis of the collecting system. In this review, we discuss recent genetic and functional evidence gathered from transgenic knockout mice and in vitro organ and cell culture implicating the RAS in the development of the ureteric bud and collecting ducts. A novel conceptual framework has emerged from this body of work which states that stroma-derived ANG II elicits activation of AT1/AT2 receptors expressed on the ureteric bud to stimulate branching morphogenesis as well as collecting duct elongation and papillogenesis.

Keywords

Kidney development Renin-angiotensin Metanephros Branching morphogenesis 

References

  1. 1.
    Saxen L (1987) Organogenesis of the kidney. Cambridge University Press, CambridgeGoogle Scholar
  2. 2.
    Al-Awqati Q, Goldberg MR (1998) Architectural patterns in branching morphogenesis in the kidney. Kidney Int 54:832–1842CrossRefGoogle Scholar
  3. 3.
    Ekblom P (1989) Developmentally regulated conversion of mesenchyme to epithelium. FASEB J 3:2141–2150PubMedGoogle Scholar
  4. 4.
    Grobstein C (1953) Inductive epithelio-mesenchymal interaction in cultured organ rudiments of the mouse metanephros. Science 118:52–55PubMedGoogle Scholar
  5. 5.
    Brenner BM, Garcia DL, Anderson S (1988) Glomeruli and blood pressure. Less of one, more the other? Am J Hypertens 1:335–347PubMedGoogle Scholar
  6. 6.
    Lisle SJ, Lewis RM, Petry CJ, Ozanne SE, Hales CN, Forhead AJ (2003) Effect of maternal iron restriction during pregnancy on renal morphology in the adult rat offspring. Br J Nutr 90:33–39CrossRefPubMedGoogle Scholar
  7. 7.
    Sainio K, Nonclercq D, Saarma M, Palgi J, Saxen L, Sariola H (1994) Neuronal characteristics in embryonic renal stroma. Int J Dev Biol 38:77–84PubMedGoogle Scholar
  8. 8.
    Mendelsohn C, Batourina E, Fung S, Gilbert T, Dodd J (1999) Stromal cells mediate retinoid-dependent functions essential for renal development. Development 126:1139–1148PubMedGoogle Scholar
  9. 9.
    Hatini A, Huh SO, Herzlinger D, Soares VC, Lai E (1996) Essential role of stromal mesenchyme in kidney morphogenesis revealed by targeted disruption of Winged Helix transcription factor BF-2. Genes Dev 10:1467–1478PubMedGoogle Scholar
  10. 10.
    Koseki C, Herzlinger D, Al-Awqati Q (1992) Apoptosis in metanephric development. J Cell Biol 119:1327–1333CrossRefPubMedGoogle Scholar
  11. 11.
    Yang J, Blum A, Novak T, Levinson R, Lai E, Barasch J (2002) An epithelial precursor is regulated by the ureteric bud and by the renal stroma. Dev Biol 246:296–310CrossRefPubMedGoogle Scholar
  12. 12.
    Arima S, Kohagura K, Abe M, Ito S (2001) Mechanisms that control glomerular hemodynamics. Clin Exp Nephrol 5:55–61CrossRefGoogle Scholar
  13. 13.
    Berry C, Touyz R, Dominiczak AF, Webb RC, Johns DG (2001) Angiotensin receptors: signaling, vascular pathophysiology, and interactions with ceramide. Am J Physiol 281:H2337-H2365Google Scholar
  14. 14.
    Wolf G, Haberstroh U, Neilson EG (1992) Angiotensin II stimulates the proliferation and biosynthesis of type I collagen in cultured murine mesangial cells. Am J Pathol 140:95–107PubMedGoogle Scholar
  15. 15.
    Goto M, Mukoyama M, Suga, Matsumoto T, Nakagawa M, Ishibashi R, Kasahara M, Sugawara A, Tanaka I, Nakao K (1997) Growth-dependent induction of angiotensin II type 2 receptor in rat mesangial cells. Hypertension 30:358–362PubMedGoogle Scholar
  16. 16.
    Gross V, Schunck WH, Honeck H, Milia AF, Kargel E, Walther T, Bader M, Inagami T, Schneider W, Luft FC (2000) Inhibition of pressure natriuresis in mice lacking the AT2 receptor. Kidney Int 57:191–202CrossRefPubMedGoogle Scholar
  17. 17.
    Siragy HM, Carey RM (1997) The subtype-2 (AT2) angiotensin receptor mediates renal production of nitric oxide in conscious rats. J Clin Invest 100:264–269PubMedGoogle Scholar
  18. 18.
    Liang P, Jones CA, Bisgrove BW, Song L, Glenn ST, Yost HJ, Gross KW (2004) Genomic characterization and expression analysis of the first nonmammalian renin genes from zebrafish and pufferfish. Physiol Genomics 16:314–322CrossRefPubMedGoogle Scholar
  19. 19.
    Wintour EM, Alcorn D, Butkus A, Congiu M, Earnest L, Pompolo S, Potocnik SJ (1996) Ontogeny of hormonal and excretory function of the meso and metanephros in the ovine fetus. Kidney Int 50:1624–1633PubMedGoogle Scholar
  20. 20.
    Celio MR, Groscurth P, Inagami T (1985) Ontogeny of renin immunoreactive cells in the human kidney. Anat Embryol (Berl) 173:49–55Google Scholar
  21. 21.
    Egerer G, Taugner R, Tiedemann K (1984) Renin immunohistochemistry in the mesonephros and metanephros of the pig embryo. Histochemistry 81:385–390CrossRefPubMedGoogle Scholar
  22. 22.
    Dressler GR, Deutsch U, Chowdhury K, Nornes HO, Gruss P (1990) Pax2, a new murine paired-box-containing gene and its expression in the developing excretory system. Development 109:787–795PubMedGoogle Scholar
  23. 23.
    Zhang SL, Moini B, Ingelfinger JR (2004) Angiotensin II increases Pax-2 expression in fetal kidney cells via the AT2 receptor. J Am Soc Nephrol 15:1452–1465CrossRefPubMedGoogle Scholar
  24. 24.
    Torres M, Gomez-Pardo E, Dressler GR, Gruss P (1995) Pax-2 controls multiple steps of urogenital development. Development 121:4057–4065PubMedGoogle Scholar
  25. 25.
    Gomez RA, Lynch KR, Sturgill BC, Elwood JP, Chevalier RL, Carey RM, Peach MJ (1989) Distribution of renin mRNA and its protein in the developing kidney. Am J Physiol 257: F850-F858PubMedGoogle Scholar
  26. 26.
    Norwood VF, Craig MR, Harris JM, Gomez RA (1997) Differential expression of angiotensin II receptors during early renal morphogenesis. Am J Physiol 272:R662-R668PubMedGoogle Scholar
  27. 27.
    Yosipiv IV, Dipp S, El-Dahr SS (1994) Ontogeny of somatic angiotensin-converting enzyme. Hypertension 23:369–374PubMedGoogle Scholar
  28. 28.
    Yosipiv IV, El-Dahr SS (1996) Activation of angiotensin-generating systems in the developing rat kidney. Hypertension 27:281–286PubMedGoogle Scholar
  29. 29.
    Jung FF, Bouyounes B, Barrio R, Tang SS, Diamant D, Ingelfinger JR (1993) Angiotensin converting enzyme in renal ontogeny: hypothesis for multiple roles. Pediatr Nephrol 7:834–840CrossRefPubMedGoogle Scholar
  30. 30.
    Prieto M, Dipp S, Meleg-Smith S, El-Dahr SS (2001) Ureteric bud derivatives express angiotensinogen and AT1 receptors. Physiol Genomics 6:29–37PubMedGoogle Scholar
  31. 31.
    Iosipiv IV, Schroeder M (2003) A role for angiotensin II AT1 receptors in ureteric bud cell branching. Am J Physiol 285:F199-F207Google Scholar
  32. 32.
    Iosipiv IV (2002) Cellular expression of the angiotensin type 2 receptor (AT2) during murine organogenesis. J Invest Medicine 50:134AGoogle Scholar
  33. 33.
    Yosypiv IV, Schroeder M (2004) Role of angiotensin type 2 (AT2) receptor in ureteric bud cell branching morphogenesis in vitro. J Am Soc Nephrol 15:419AGoogle Scholar
  34. 34.
    Kakuchi J, Ichiki T, Kiyama S, Hogan BL, Fogo A, Inagami T, Ichikawa I (1995) Developmental expression of renal angiotensin II receptor genes in the mouse. Kidney Int 47:140–147PubMedGoogle Scholar
  35. 35.
    Garcia-Villalba P, Denkers ND, Wittwer CT, Wittwer CT, Hoff C, Nelson RD, Mauch TJ (2003) Real-time PCR quantification of AT1 and AT2 angiotensin receptor mRNA expression in the developing rat kidney. Nephron. Exp Nephrol 94:e154–159CrossRefGoogle Scholar
  36. 36.
    Lopez ML, Pentz ES, Robert B, Abrahamson DR, Gomez RA (2001) Embryonic origin and lineage of juxtaglomerular cells. Am J Physiol 281:F345-F356Google Scholar
  37. 37.
    Yoo KH, Wolstenholme JT, Chevalier RL (1997) Angiotensin-converting enzyme inhibition decreases growth factor expression in the neonatal rat kidney. Pediatr Res 42:588–592PubMedGoogle Scholar
  38. 38.
    Tufro-McReddie A, Romano LM, Harris JM, Ferder L, Gomez RA (1995) Angiotensin II regulates nephrogenesis and renal vascular development. Am J Physiol 38:F110-F115Google Scholar
  39. 39.
    Friberg P, Sundelin B, Bohman SO, Bobik A, Nilsson H, Wickman A, Gustafsson H, Petersen J, Adams MA (1994) Renin-angiotensin system in neonatal rats: induction of a renal abnormality in response to ACE inhibition or angiotensin II antagonism. Kidney Int 45:485–492PubMedGoogle Scholar
  40. 40.
    Schaefer C (2003) Angiotensin II-receptor-antagonists: further evidence of fetotoxicity but not teratogenicity. Birth Defects Res A Clin Mol Teratol 67:591–594CrossRefPubMedGoogle Scholar
  41. 41.
    Tabacova S, Little R, Tsong Y, Vega A, Kimmel CA (2003) Adverse pregnancy outcomes associated with maternal enalapril antihypertensive treatment. Pharmacoepidemiol Drug Saf 12:633–646CrossRefPubMedGoogle Scholar
  42. 42.
    Nagata M, Tanimoto K, Fukamizu A, Kon Y, Sugiyama F, Yagami K, Murakami K, Watanabe T (1996) Nephrogenesis and renovascular development in angiotensinogen-deficient mice. Lab Invest 75:745–753PubMedGoogle Scholar
  43. 43.
    Niimura F, Labosky PA, Kakuchi J, Okubo S, Yoshida H, Oikawa T, Ichiki T, Naftilan AJ, Fogo A, Inagami T (1995) Gene targeting in mice reveals a requirement for angiotensin in the development and maintenance of kidney morphology and growth factor regulation. J Clin Invest 96:2947–2954PubMedGoogle Scholar
  44. 44.
    Takahashi N, Lopez ML, Cowhig JE Jr, Taylor MA, Hatada T, Riggs E, Lee G, Gomez RA, Kim HS, Smithies O (2005) Ren1c homozygous null mice are hypotensive and polyuric, but heterozygotes are indistinguishable from wild-type. J Am Soc Nephrol 16125–132Google Scholar
  45. 45.
    Esther CR Jr, Howard TE, Marino EM, Goddard JM, Capecchi MR, Bernstein KE (1996) Mice lacking angiotensin-converting enzyme have low blood pressure, renal pathology, and reduced male fertility. Lab Invest 7:953–965Google Scholar
  46. 46.
    Oliverio MI, Kim HS, Ito M, Le T, Audoly L, Best CF, Hiller S, Kluckman K, Maeda N, Smithies O, Coffman TM (1998) Reduced growth, abnormal kidney structure, and type 2 (AT2) angiotensin receptor-mediated blood pressure regulation in mice lacking both AT1A and AT1B receptors for angiotensin II. Proc Natl Acad Sci USA 95:15496–15501CrossRefPubMedGoogle Scholar
  47. 47.
    Tsuchida S, Matsusaka T, Chen X, Okubo S, Niimura F, Nishimura H, Fogo A, Utsunomiya H, Inagami T, Ichikawa I (1998) Murine double nullizygotes of the angiotensin type 1A and 1B receptor genes duplicate severe abnormal phenotypes of angiotensinogen nullizygotes. J Clin Invest 101:755–760PubMedGoogle Scholar
  48. 48.
    Okubo S, Niimura F, Matsusaka T, Fogo A, Hogan BL, Ichikawa I (1998) Angiotensinogen gene null-mutant mice lack homeostatic regulation of glomerular filtration and tubular reabsorption. Kidney Int 53:617–625CrossRefPubMedGoogle Scholar
  49. 49.
    Oshima K, Miyazaki Y, Brock JW, Adams MC, Ichikawa I, Pope JC 4th (2001) Angiotensin type II receptor expression and ureteral budding. J Urol 166:1848–1852CrossRefPubMedGoogle Scholar
  50. 50.
    Nishimura H, Yerkes E, Hohenfellner K, Miyazaki Y, Ma J, Hunley TE, Yoshida H, Ichiki T, Threadgill D, Phillips JA 3rd, Hogan BM, Fogo A, Brock JW 3rd, Inagami T, Ichikawa I (1999) Role of the angiotensin type 2 receptor gene in congenital anomalies of the kidney and urinary tract, CAKUT, of mice and men. Mol Cell 3:1–10CrossRefPubMedGoogle Scholar
  51. 51.
    Bouchard M (2004) Transcriptional control of kidney development. Differentiation 72:295–306CrossRefPubMedGoogle Scholar
  52. 52.
    Ray S, Sherman CT, Lu M, Brasier AR (2002) Angiotensinogen gene expression is dependent on signal transducer and activator of transcription 3-mediated p300/cAMP response element binding protein-binding protein coactivator recruitment and histone acetyltransferase activity. Mol Endocrinol 16:824–836CrossRefPubMedGoogle Scholar
  53. 53.
    Guo Y, Mascareno E, Siddiqui MA (2004) Distinct components of Janus kinase/signal transducer and activator of transcription signaling pathway mediate the regulation of systemic and tissue localized renin-angiotensin system. Mol Endocrinol 18:1033–1041CrossRefPubMedGoogle Scholar
  54. 54.
    Date S, Nibu Y, Yanai K, Hirata J, Yagami K, Fukamizu A (2004) Finb, a multiple zinc finger protein, represses transcription of the human angiotensinogen gene. Int J Mol Med 13:637–642PubMedGoogle Scholar
  55. 55.
    Jamaluddin M, Meng T, Sun J, Boldogh I, Han Y, Brasier AR (2000) Angiotensin II induces nuclear factor (NF)-kappaB1 isoforms to bind the angiotensinogen gene acute-phase response element: a stimulus-specific pathway for NF-kappaB activation. Mol Endocrinol 14:99–113CrossRefPubMedGoogle Scholar
  56. 56.
    Philippe J, Drucker DJ, Habener JF (1987) Glucagon gene transcription in an islet cell line is regulated via a protein kinase C-activated pathway. J Biol Chem 262:1823–1828Google Scholar
  57. 57.
    Wang TT, Chen X, Wu XH, Zhang SL, Chan JS (1999) Molecular mechanism(s) of action of isoproterenol on the expression of the angiotensinogen gene in opossum kidney proximal tubular cells. Kidney Int 55:1713–1723CrossRefPubMedGoogle Scholar
  58. 58.
    Lin KH, Lee HY, Shih CH, Yen CC, Chen SL, Yang RC, Wang CS (2003) Plasma protein regulation by thyroid hormone. J Endocrinol 179:367–377CrossRefPubMedGoogle Scholar
  59. 59.
    Harte AL, McTernan PG, McTernan CL, Crocker J, Starcynski J, Barnett AH, Matyka K, Kumar S (2003) Insulin increases angiotensinogen expression in human abdominal subcutaneous adipocytes. Diabetes Obes Metab 5:462–467CrossRefPubMedGoogle Scholar
  60. 60.
    Li YC, Kong J, Wei M, Chen ZF, Liu SQ, Cao LP (2002) 1,25-Dihydroxyvitamin D(3) is a negative endocrine regulator of the renin-angiotensin system. J Clin Invest 110:229–238CrossRefPubMedGoogle Scholar
  61. 61.
    Shi Q, Gross KW, Sigmund CD (2001) Retinoic acid-mediated activation of the mouse renin enhancer. J Biol Chem 276:3597–3603Google Scholar
  62. 62.
    Klar J, Vitzthum H, Kurtz A (2004) Aldosterone enhances renin gene expression in juxtaglomerular cells. Am J Physiol 286:F349-F355CrossRefGoogle Scholar
  63. 63.
    Takeda K, Ichiki T, Funakoshi Y, Ito K, Takeshita A (2000) Downregulation of angiotensin II type 1 receptor by all-trans retinoic acid in vascular smooth muscle cells. Hypertension 35:297–302PubMedGoogle Scholar
  64. 64.
    Vilar J, Gilbert T, Moreau E, Merlet-Benichou C (1996) Metanephros organogenesis is highly stimulated by vitamin A derivatives in organ culture. Kidney Int 49:1478–1487PubMedGoogle Scholar
  65. 65.
    Zhang H, Palmer R, Gao X, Kreidberg J, Gerald W, Hsiao L, Jensen RV, Gullans SR, Haber DA (2003) Transcriptional activation of placental growth factor by the forkhead/winged helix transcription factor FoxD1. Curr Biol 13:1625–1629CrossRefPubMedGoogle Scholar
  66. 66.
    Miyazaki Y, Tsuchida S, Fogo A, Ichikawa I (1999) The renal lesions that develop in neonatal mice during angiotensin inhibition mimic obstructive nephropathy. Kidney Int 55:1683–1695CrossRefPubMedGoogle Scholar
  67. 67.
    Qiao J, Uzzo R, Obara-Ishohara T, Degenstein L, Fuchs E, Herzlinger D (1999) FGF-7 modulates ureteric bud growth and nephron number in the developing kidney. Development 126:547–554PubMedGoogle Scholar
  68. 68.
    Qiao J, Bush KT, Steer DL, Stuart RO, Sakurai H, Wachsman W, Nigam SK (2001) Multiple fibroblast growth factors support growth of the ureteric bud but have different effects on branching morphogenesis. Mech Dev 109:123–135CrossRefPubMedGoogle Scholar
  69. 69.
    Stirling D, Magness RR, Stone R, Waterman MR, Simpson ER (1990) Angiotensin II inhibits luteinizing hormone-stimulated cholesterol side chain cleavage expression and stimulates basic fibroblast growth factor expression in bovine luteal cells in primary culture. J Biol Chem 265:5–8Google Scholar
  70. 70.
    Ohuchi H, Hori Y, Yamasaki M, Harada H, Sekine K, Kato S, Itoh N (2000) FGF10 acts as a major ligand for FGF receptor 2IIIb in mouse multi-organ development. Biochem Biophys Res Commun 277:643–649Google Scholar
  71. 71.
    Cano-Gauci DF, Song H, Yang H, McKerlie C, Choo B, Shi W, Pullano R, Piscione TD, Grisaru S, Soon S, Sedlackova L, Tanswell AK, Mak TW, Yeger H, Lockwood GA, Rosenblum ND, Filmus J (1999) Glypican 3-deficient mice exhibit developmental overgrowth and some of the renal abnormalities typical of Simpson-Golabi-Behmel syndrome. J Cell Biol 146:255–264PubMedGoogle Scholar
  72. 72.
    Zhang P, Liegeois NJ, Wong C, Finegold M, Hou H, Thompson JC, Silverman A, Harper JW, DePinho RA, Elledge SJ (1997) Altered cell differentiation and proliferation in mice lacking p57KIP2 indicates a role in Beckwith-Wiedemann syndrome. Nature 387:151–158CrossRefPubMedGoogle Scholar
  73. 73.
    Stoll M, Steckelings UM, Paul M, Bottari SP, Metzger R, Unger T (1995) The angiotensin AT2-receptor mediates inhibition of cell proliferation in coronary endothelial cells. J Clin Invest 95:651–657PubMedGoogle Scholar
  74. 74.
    AbdAlla S, Lother H, Abdel-tawab AM, Quitterer U (2001) The angiotensin II AT2 receptor is an AT1 receptor antagonist. J Biol Chem 276:39721–39726Google Scholar
  75. 75.
    Gendron L, Payet MD, Gallo-Payet N (2003) The angiotensin type 2 receptor of angiotensin II and neuronal differentiation: from observations to mechanisms. J Mol Endocrinol 31:359–372CrossRefPubMedGoogle Scholar
  76. 76.
    Huwiler A, Stabel S, Fabbro D, Pfeilschifter (1995) Platelet-derived growth factor and angiotensin II stimulate the mitogen-activated protein kinase cascade in renal mesangial cells: comparison of hypertrophic and hyperplastic agonists. Biochem J 305:777–784PubMedGoogle Scholar
  77. 77.
    Saward, L, Zahradka P (1997) Angiotensin II activates phosphatidylinositol 3-kinase in vascular smooth muscle cells. Circ Res 81:249–257PubMedGoogle Scholar
  78. 78.
    Schorb W, Peeler TC, Madigan NN, Conrad KM, Baker KM (1994) Angiotensin II-induced protein tyrosine phosphorylation in neonatal rat cardiac fibroblasts. J Biol Chem 269:19626–19632Google Scholar
  79. 79.
    Karihaloo A, O’Rourke DA, Nickel C, Spokes K, Cantley LG (2001) Differential MAPK pathways utilized for HGF- and EGF-dependent renal epithelial morphogenesis. J Biol Chem 276:9166–9173Google Scholar
  80. 80.
    Tang MJ, Cai Y, Tsai SJ, Wang YK, Dressler GR (2002) Ureteric bud outgrowth in response to RET activation is mediated by phosphatidylinositol 3-kinase. Dev Biol 243:128–136CrossRefPubMedGoogle Scholar
  81. 81.
    Eguchi S, Numaguchi K, Iwasaki H, Matsumoto T, Yamakawa T, Utsunomiya H, Motley ED, Kawakatsu H, Owada KM, Hirata Y, Marumo F, Inagami T (1998) Calcium-dependent epidermal growth factor receptor transactivation mediates the angiotensin II-induced mitogen-activated protein kinase activation in vascular smooth muscle cells. J Biol Chem 273:8890–8896Google Scholar
  82. 82.
    Seta K, Sadoshima J (2003) Phosphorylation of tyrosine 319 of the angiotensin II type 1 receptor mediates angiotensin II-induced trans-activation of the epidermal growth factor receptor. J Biol Chem 278:9019–9026Google Scholar
  83. 83.
    Yosypiv IV, Schroeder M (2003) Angiotensin (ANG) II stimulates ureteric bud (UB) cell branching morphogenesis in vitro via transactivation of epidermal growth factor receptor (EGFR). J Am Soc Nephrol 14:98ACrossRefGoogle Scholar
  84. 84.
    Rocic P, Govindarajan G, Sabri A, Lucchesi PA (2001) A role for PYK2 in regulation of ERK1/2 MAP kinases and PI 3-kinase by ANG II in vascular smooth muscle. Am J Physiol 280:C90–99PubMedGoogle Scholar
  85. 85.
    Schafer B, Gschwind A, Ullrich A (2004) Multiple G-protein-coupled receptor signals converge on the epidermal growth factor receptor to promote migration and invasion. Oncogene 23:991–999CrossRefPubMedGoogle Scholar
  86. 86.
    Horiuchi M, Akishita M, Dzau VJ (1998) Molecular and cellular mechanism of angiotensin II-mediated apoptosis. Endocr Res 24:307–314PubMedGoogle Scholar
  87. 87.
    Fukizawa J, Booz GW, Hunt RA, Shimizu N, Karoor V, Baker KM, Dostal DE (2000) Cardiotrophin-1 increases angiotensinogen mRNA in rat cardiac myocytes through STAT3: an autocrine loop for hypertrophy. Hypertension 35:1191–1196PubMedGoogle Scholar

Copyright information

© IPNA 2005

Authors and Affiliations

  1. 1.Section of Pediatric Nephrology, Department of PediatricsTulane University Health Sciences CenterNew OrleansUSA

Personalised recommendations