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Evolving concepts on regulation and function of renin in distal nephron

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Abstract

Sustained stimulation of the intrarenal/intratubular renin–angiotensin system in a setting of elevated arterial pressure elicits renal vasoconstriction, increased sodium reabsorption, proliferation, fibrosis, and eventual renal injury. Activation of luminal AT1 receptors in proximal and distal nephron segments by local Ang II formation stimulates various transport systems. Augmented angiotensinogen (AGT) production by proximal tubule cells increases AGT secretion contributing to increased proximal Ang II levels and leading to spillover of AGT into the distal nephron segments, as reflected by increased urinary AGT excretion. The increased distal delivery of AGT provides substrate for renin, which is expressed in principal cells of the collecting tubule and collecting ducts, and is also stimulated by AT1 receptor activation. Renin and prorenin are secreted into the tubular lumen and act on the AGT delivered from the proximal tubule to form more Ang I. The catalytic actions of renin and or prorenin may be enhanced by binding to prorenin receptors on the intercalated cells or soluble prorenin receptor secreted into the tubular fluid. There is also increased luminal angiotensin converting enzyme in collecting ducts facilitating Ang II formation leading to stimulation of sodium reabsorption via sodium channel and sodium/chloride co-transporter. Thus, increased collecting duct renin contributes to Ang II-dependent hypertension by augmenting distal nephron intratubular Ang II formation leading to sustained stimulation of sodium reabsorption and progression of hypertension.

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References

  1. Advani A, Kelly DJ, Cox AJ, White KE, Advani SL, Thai K, Connelly KA, Yuen D, Trogadis J, Herzenberg AM, Kuliszewski MA, Leong-Poi H, Gilbert RE (2009) The (Pro)renin receptor: site-specific and functional linkage to the vacuolar H+-ATPase in the kidney. Hypertension 54:261–269

    Article  PubMed  CAS  Google Scholar 

  2. Ashek A, Menzies RI, Mullins LJ, Bellamy CO, Harmar AJ, Kenyon CJ, Flatman PW, Mullins JJ, Bailey MA (2012) Activation of thiazide-sensitive co-transport by angiotensin II in the cyp1a1-Ren2 hypertensive rat. PLoS One 7:e36311

    Article  PubMed  CAS  Google Scholar 

  3. Beutler KT, Masilamani S, Turban S, Nielsen J, Brooks HL, Ageloff S, Fenton RA, Packer RK, Knepper MA (2003) Long-term regulation of ENaC expression in kidney by angiotensin II. Hypertension 41:1143–1150

    Article  PubMed  CAS  Google Scholar 

  4. Braam B, Navar LG, Mitchell KD (1995) Modulation of tubuloglomerular feedback by angiotensin II type 1 receptors during the development of Goldblatt hypertension. Hypertension 25:1232–1237

    Article  PubMed  CAS  Google Scholar 

  5. Brosnihan KB, Neves LA, Joyner J, Averill DB, Chappell MC, Sarao R, Penninger J, Ferrario CM (2003) Enhanced renal immunocytochemical expression of ANG-(1–7) and ACE2 during pregnancy. Hypertension 42:749–753

    Article  PubMed  CAS  Google Scholar 

  6. Casarini DE, Boim MA, Stella RCR, Krieger-Azzolini MH, Krieger JE, Schor N (1997) Angiotensin I-converting enzyme activity in tubular fluid along the rat nephron. Am J Physiol Renal Physiol 272:F405–F409

    CAS  Google Scholar 

  7. Castrop H, Hocherl K, Kurtz A, Schweda F, Todorov V, Wagner C (2010) Physiology of kidney renin. Physiol Rev 90:607–673

    Article  PubMed  CAS  Google Scholar 

  8. Catanzaro DF (2005) Physiological relevance of renin/prorenin binding and uptake. Hypertens Res 28:97–105

    Article  PubMed  CAS  Google Scholar 

  9. Catanzaro DF, Mullins JJ, Morris BJ (1983) The biosynthetic pathway of renin in mouse submandibular gland. J Biol Chem 258:7364–7368

    PubMed  CAS  Google Scholar 

  10. Celio MR, Inagami T (1981) Angiotensin II immunoreactivity co-exists with renin in the juxtaglomerular granular cells of the kidney. Proc Natl Acad Sci USA 78:3897–3900

    Article  PubMed  CAS  Google Scholar 

  11. Cervenka L, Wang C-T, Mitchell KD, Navar LG (1999) Proximal tubular angiotensin II levels and renal functional responses to AT1 receptor blockade in nonclipped kidneys of Goldblatt hypertensive rats. Hypertension 33:102–107

    Article  PubMed  CAS  Google Scholar 

  12. Chen M, Harris MP, Rose D, Smart A, He XR, Kretzler M, Briggs JP, Schnermann J (1994) Renin and renin mRNA in proximal tubules of the rat kidney. J Clin Invest 94:237–243

    Article  PubMed  CAS  Google Scholar 

  13. Chou CL, Rapko SI, Knepper MA (1998) Phosphoinositide signaling in rat inner medullary collecting duct. Am J Physiol 274:F564–F572

    PubMed  CAS  Google Scholar 

  14. Danser AHJ, van Kats JP, Admiraal PJJ, Derkx FHM, Lamers JMJ, Verdouw PD, Saxena PR, Schalekamp MADH (1994) Cardiac renin and angiotensins. Uptake from plasma versus in situ synthesis. Hypertension 24:37–48

    Article  PubMed  CAS  Google Scholar 

  15. DeForrest J, Knappenberger R, Antonaccio M, Ferrone R, Creekmore J (1982) Angiotensin II is a necessary component for the development of hypertension in the two kidney, one clip rat. Am J Cardiol 49:1515–1517

    Article  PubMed  CAS  Google Scholar 

  16. Deinum J, Ronn B, Mathiesen E, Derkx FH, Hop WC, Schalekamp MA (1999) Increase in serum prorenin precedes onset of microalbuminuria in patients with insulin-dependent diabetes mellitus. Diabetologia 42:1006–1010

    Article  PubMed  CAS  Google Scholar 

  17. Deinum J, Tarnow L, van Gool JM, de Bruin RA, Derkx FH, Schalekamp MA, Parving HH (1999) Plasma renin and prorenin and renin gene variation in patients with insulin-dependent diabetes mellitus and nephropathy. Nephrol Dial Transplant 14:1904–1911

    Article  PubMed  CAS  Google Scholar 

  18. Dzau VJ, Ellison KE, Brody T, Ingelfinger J, Pratt RE (1987) A comparative study of the distributions of renin and angiotensinogen messenger ribonucleic acids in rat and mouse tissues. Endocrinology 120:2334–2338

    Article  PubMed  CAS  Google Scholar 

  19. Ekker M, Tronik D, Rougeon F (1989) Extra-renal transcription of the renin genes in multiple tissues of mice and rats. Proc Natl Acad Sci USA 86:5155–5158

    Article  PubMed  CAS  Google Scholar 

  20. Eladari D, Chambrey R, Peti-Peterdi J (2012) A new look at electrolyte transport in the distal tubule. Annu Rev Physiol 74:325–349

    Article  PubMed  CAS  Google Scholar 

  21. Field LJ, McGowan RA, Dickinson DP, Gross KW (1984) Tissue and gene specificity of mouse renin expression. Hypertension 6:597–603

    Article  PubMed  CAS  Google Scholar 

  22. Gallagher PE, Chappell MC, Ferrario CM, Tallant EA (2006) Distinct roles for ANG II and ANG-(1–7) in the regulation of angiotensin-converting enzyme 2 in rat astrocytes. Am J Physiol Cell Physiol 290:C420–C426

    Article  PubMed  CAS  Google Scholar 

  23. Gilbert RE, Wu LL, Kelly DJ, Cox A, Wilkinson-Berka JL, Johnston CI, Cooper ME (1999) Pathological expression of renin and angiotensin II in the renal tubule after subtotal nephrectomy. Implications for the pathogenesis of tubulointerstitial fibrosis. Am J Pathol 155:429–440

    Article  PubMed  CAS  Google Scholar 

  24. Gomez RA, Lynch KR, Chevalier RL, Everett AD, Johns DW, Wilfong N, Peach MJ, Carey RM (1988) Renin and angiotensinogen gene expression and intrarenal renin distribution during ACE inhibition. Am J Physiol Renal Physiol 254:F900–F906

    CAS  Google Scholar 

  25. Gonzalez AA, Lara LS, Luffman C, Seth DM, Prieto MC (2011) Soluble form of the (pro)renin receptor is augmented in the collecting duct and urine of chronic angiotensin II-dependent hypertensive rats. Hypertension 57:859–864

    Article  PubMed  CAS  Google Scholar 

  26. Gonzalez AA, Liu L, Lara LS, Seth DM, Navar LG, Prieto MC (2011) Angiotensin II stimulates renin in inner medullary collecting duct cells via protein kinase C and independent of epithelial sodium channel and mineralocorticoid receptor activity. Hypertension 57:594–599

    Article  PubMed  CAS  Google Scholar 

  27. Gonzalez-Villalobos RA, Satou R, Ohashi N, Semprun-Prieto LC, Katsurada A, Kim C, Upchurch GM, Prieto MC, Kobori H, Navar LG (2010) Intrarenal mouse renin–angiotensin system during ANG II-induced hypertension and ACE inhibition. Am J Physiol Renal Physiol 298:F150–F157

    Article  PubMed  CAS  Google Scholar 

  28. Guan S, Fox J, Mitchell KD, Navar LG (1992) Angiotensin and angiotensin converting enzyme tissue levels in two-kidney, one clip hypertensive rats. Hypertension 20:763–767

    Article  PubMed  CAS  Google Scholar 

  29. Hackenthal E, Paul M, Ganten D, Taugner R (1990) Morphology, physiology, and molecular biology of renin secretion. Physiol Rev 70:1067–1116

    PubMed  CAS  Google Scholar 

  30. Henrich WL, McAllister EA, Eskue A, Miller T, Moe OW (1996) Renin regulation in cultured proximal tubular cells. Hypertension 27:1337–1340

    Article  PubMed  CAS  Google Scholar 

  31. Huang W-C, Bell PD, Harvey D, Mitchell KD, Navar LG (1988) Angiotensin influences on tubuloglomerular feedback mechanism in hypertensive rats. Kidney Int 34:631–637

    Article  PubMed  CAS  Google Scholar 

  32. Huang W-C, Navar LG (1983) Effects of unclipping and converting enzyme inhibition on bilateral renal function in 2 kidney 1 clip Goldblatt hypertensive rats. Kidney Int 23:816–822

    Article  PubMed  CAS  Google Scholar 

  33. Huang W-C, Ploth DW, Bell PD, Work J, Navar LG (1981) Bilateral renal function responses to converting enzyme inhibitor (SQ 20881) in two kidney one clip Goldblatt hypertensive rats. Hypertension 3:285–293

    Article  PubMed  CAS  Google Scholar 

  34. Ichihara A, Hayashi M, Kaneshiro Y, Suzuki F, Nakagawa T, Tada Y, Koura Y, Nishiyama A, Okada H, Uddin MN, Nabi AH, Ishida Y, Inagami T, Saruta T (2004) Inhibition of diabetic nephropathy by a decoy peptide corresponding to the "handle" region for nonproteolytic activation of prorenin. J Clin Invest 114:1128–1135

    PubMed  CAS  Google Scholar 

  35. Ichihara A, Sakoda M, Kurauchi-Mito A, Kaneshiro Y, Itoh H (2008) Involvement of (pro)renin receptor in the glomerular filtration barrier. J Mol Med 86:629–635

    Article  PubMed  CAS  Google Scholar 

  36. Imamura A, Mackenzie HS, Lacy ER, Hutchison FN, Fitzgibbon WR, Ploth DW (1995) Effects of chronic treatment with angiotensin converting enzyme inhibitor or an angiotensin receptor antagonist in two-kidney, one-clip hypertensive rats. Kidney Int 47:1394–1402

    Article  PubMed  CAS  Google Scholar 

  37. Ingert C, Grima M, Coquard C, Barthelmebs M, Imbs JL (2002) Contribution of angiotensin II internalization to intrarenal angiotensin II levels in rats. Am J Physiol Renal Physiol 283:F1003–F1010

    PubMed  Google Scholar 

  38. Ishiyama Y, Gallagher PE, Averill DB, Tallant EA, Brosnihan KB, Ferrario CM (2004) Upregulation of angiotensin-converting enzyme 2 after myocardial infarction by blockade of angiotensin II receptors. Hypertension 43:970–976

    Article  PubMed  CAS  Google Scholar 

  39. Iwai N, Inagami T (1992) Quantitative analysis of renin gene expression in extrarenal tissues by polymerase chain reaction method. J Hypertens 10:717–724

    PubMed  CAS  Google Scholar 

  40. Jan Danser AH, Batenburg WW, van Esch JH (2007) Prorenin and the (pro)renin receptor—an update. Nephrol Dial Transplant 22:1288–1292

    Article  PubMed  CAS  Google Scholar 

  41. Kaneshiro Y, Ichihara A, Takemitsu T, Sakoda M, Suzuki F, Nakagawa T, Hayashi M, Inagami T (2006) Increased expression of cyclooxygenase-2 in the renal cortex of human prorenin receptor gene-transgenic rats. Kidney Int 70:641–646

    Article  PubMed  CAS  Google Scholar 

  42. Kang JJ, Toma I, Sipos A, Meer EJ, Vargas SL, Peti-Peterdi J (2008) The collecting duct is the major source of prorenin in diabetes. Hypertension 51:1597–1604

    Article  PubMed  CAS  Google Scholar 

  43. Klar J, Sigl M, Obermayer B, Schweda F, Kramer BK, Kurtz A (2005) Calcium inhibits renin gene expression by transcriptional and posttranscriptional mechanisms. Hypertension 46:1340–1346

    Article  PubMed  CAS  Google Scholar 

  44. Kobori H, Harrison-Bernard LM, Navar LG (2001) Enhancement of angiotensinogen expression in angiotensin II-dependent hypertension. Hypertension 37:1329–1335

    Article  PubMed  CAS  Google Scholar 

  45. Kobori H, Harrison-Bernard LM, Navar LG (2002) Urinary excretion of angiotensinogen reflects intrarenal angiotensinogen production. Kidney Int 61:579–585

    Article  PubMed  CAS  Google Scholar 

  46. Kobori H, Nangaku M, Navar LG, Nishiyama A (2007) The intrarenal renin–angiotensin system: from physiology to the pathobiology of hypertension and kidney disease. Pharmacol Rev 59:251–287

    Article  PubMed  CAS  Google Scholar 

  47. Koka V, Huang XR, Chung AC, Wang W, Truong LD, Lan HY (2008) Angiotensin II up-regulates angiotensin I-converting enzyme (ACE), but down-regulates ACE2 via the AT1-ERK/p38 MAP kinase pathway. Am J Pathol 172:1174–1183

    Article  PubMed  CAS  Google Scholar 

  48. Komlosi P, Fuson AL, Fintha A, Peti-Peterdi J, Rosivall L, Warnock DG, Bell PD (2003) Angiotensin I conversion to angiotensin II stimulates cortical collecting duct sodium transport. Hypertension 42:195–199

    Article  PubMed  CAS  Google Scholar 

  49. Krebs C, Hamming I, Sadaghiani S, Steinmetz OM, Meyer-Schwesinger C, Fehr S, Stahl RA, Garrelds IM, Danser AH, van Goor H, Contrepas A, Nguyen G, Wenzel U (2007) Antihypertensive therapy upregulates renin and (pro)renin receptor in the clipped kidney of Goldblatt hypertensive rats. Kidney Int 72:725–730

    Article  PubMed  CAS  Google Scholar 

  50. Lai KN, Leung JCK, Lai KB, To WY, Yeung VTF, Lai FMM (1998) Gene expression of the renin–angiotensin system in human kidney. J Hypertens 16:91–102

    Article  PubMed  CAS  Google Scholar 

  51. Lalouel J-M, Rohrwasser A, Terreros D, Morgan T, Ward K (2001) Angiotensinogen in essential hypertension: from genetics to nephrology. J Am Soc Nephrol 12:606–615

    PubMed  CAS  Google Scholar 

  52. Lantelme P, Rohrwasser A, Gociman B, Hillas E, Cheng T, Petty G, Thomas J, Xiao S, Ishigami T, Herrmann T, Terreros DA, Ward K, Lalouel JM (2002) Effects of dietary sodium and genetic background on angiotensinogen and renin in mouse. Hypertension 39:1007–1014

    Article  PubMed  CAS  Google Scholar 

  53. Leyssac PP (1986) Changes in single nephron renin release are mediated by tubular fluid flow rate. Kidney Int 30:332–339

    Article  PubMed  CAS  Google Scholar 

  54. Liu L, Gonzalez AA, McCormack M, Seth DM, Kobori H, Navar LG, Prieto MC (2011) Increased renin excretion associated with augmented urinary angiotensin (Ang) II levels in chronic angiotensin II-infused hypertensive rats. Am J Physiol Renal Physiol 301:F1195–F1201

    Article  PubMed  CAS  Google Scholar 

  55. Mamenko M, Zaika O, Ilatovskaya DV, Staruschenko A, Pochynyuk O (2012) Angiotensin II increases activity of the epithelial Na+ channel (ENaC) in distal nephron additively to aldosterone. J Biol Chem 287:660–671

    Article  PubMed  CAS  Google Scholar 

  56. Masilamani S, Kim GH, Mitchell C, Wade JB, Knepper MA (1999) Aldosterone-mediated regulation of ENaC alpha, beta, and gamma subunit proteins in rat kidney [see comments]. J Clin Invest 104:R19–R23

    Article  PubMed  CAS  Google Scholar 

  57. Matsusaka T, Niimura F, Shimizu A, Pastan I, Saito A, Kobori H, Nishiyama A, Ichikawa I (2012) Liver angiotensinogen is the primary source of renal angiotensin II. J Am Soc Nephrol 23:1181–1189

    Article  PubMed  CAS  Google Scholar 

  58. Menard J, N'Goc PW, Bariety J, Guyenne PT, Corvol P (1979) Direct radioimmunoassay and immunocytochemical localization of renin in human kidneys. Clin Sci (Lond) 57(Suppl 5):105s–108s

    Google Scholar 

  59. Mendelsohn FAO (1980) Failure of suppression of intrarenal angiotensin II in the contralateral kidney of one clip, two kidney hypertensive rats. Clin Exp Pharmacol Physiol 7:219–223

    Article  PubMed  CAS  Google Scholar 

  60. Milani CJ, Kobori H, Mullins JJ, Mitchell KD (2010) Enhanced urinary angiotensinogen excretion in Cyp1a1-Ren2 transgenic rats with inducible ANG II-dependent malignant hypertension. Am J Med Sci 340:389–394

    Article  PubMed  Google Scholar 

  61. Mitchell KD, Navar LG (1995) Intrarenal actions of angiotensin II in the pathogenesis of experimental hypertension. In: Laragh JH, Brenner BM (eds) Hypertension: Pathophysiology, diagnosis, and management. Raven, New York, pp 1437–1450

    Google Scholar 

  62. Moe OW, Ujiie K, Star RA, Miller RT, Widell J, Alpern RJ, Henrich WL (1993) Renin expression in renal proximal tubule. J Clin Invest 91:774–779

    Article  PubMed  CAS  Google Scholar 

  63. Morgan T, Davis JM (1975) Renin secretion at the individual nephron level. Pflügers Arch 359:23–31

    Article  PubMed  CAS  Google Scholar 

  64. Morgan T, Gillies A (1977) Factors controlling the release of renin: a micropuncture study in the cat. Pflügers Arch 368:13–18

    Article  PubMed  CAS  Google Scholar 

  65. Morishita R, Higaki J, Okunishi H, Tanaka T, Ishii K, Nagano M, Mikami H, Ogihara T, Murakami K, Miyazaki M (1991) Changes in gene expression of the renin–angiotensin system in two-kidney, one clip hypertensive rats. J Hypertens 9:187–192

    Article  PubMed  CAS  Google Scholar 

  66. Morton JJ, Wallace ECH (1983) The importance of the renin–angiotensin system in the development and maintenance of hypertension in the two-kidney, one-clip hypertensive rat. Clin Sci (Lond) 64:359–370

    CAS  Google Scholar 

  67. Muller DN, Klanke B, Feldt S, Cordasic N, Hartner A, Schmieder RE, Luft FC, Hilgers KF (2008) (Pro)renin receptor peptide inhibitor "handle-region" peptide does not affect hypertensive nephrosclerosis in Goldblatt rats. Hypertension 51:676–681

    Article  PubMed  CAS  Google Scholar 

  68. Muller MW, Todorov V, Kramer BK, Kurtz A (2002) Angiotensin II inhibits renin gene transcription via the protein kinase C pathway. Pflugers Arch 444:499–505

    Article  PubMed  CAS  Google Scholar 

  69. Naruse M, Takii Y, Inagami T (1981) Renin exists in high concentration in the adrenal gland of the rat. Biomed Res 2:583–586

    CAS  Google Scholar 

  70. Navar LG, Harrison-Bernard LM, Imig JD (1998) Compartmentalization of intrarenal angiotensin II. In: Ulfendahl HR, Aurell M (eds) Renin–angiotensin. Portland, London, pp 193–208

    Google Scholar 

  71. Navar LG, Harrison-Bernard LM, Wang C-T, Cervenka L, Mitchell KD (1999) Concentrations and actions of intraluminal angiotensin II. J Am Soc Nephrol 10:S189–S195

    PubMed  CAS  Google Scholar 

  72. Navar LG, Imig JD, Zou L, Wang C-T (1997) Intrarenal production of angiotensin II. Semin Nephrol 17:412–422

    PubMed  CAS  Google Scholar 

  73. Navar LG, Kobori H, Prieto MC, Gonzalez-Villalobos RA (2011) Intratubular renin–angiotensin system in hypertension. Hypertension 57:355–362

    Article  PubMed  CAS  Google Scholar 

  74. Navar LG, Ploth DW (2008) Pathophysiology of renovascular hypertension. In: Izzo JL, Black HR, Sica DA (eds) Hypertension primer: the essentials of high blood pressure. Lippincott Williams & Wilkins, Philadelphia, pp 162–165

    Google Scholar 

  75. Navar LG, Prieto MC, Satou R, Kobori H (2011) Intrarenal angiotensin II and its contribution to the genesis of chronic hypertension. Curr Opin Pharmacol 11:180–186

    Article  PubMed  CAS  Google Scholar 

  76. Nguyen G (2006) Renin/prorenin receptors. Kidney Int 69:1503–1506

    Article  PubMed  CAS  Google Scholar 

  77. Nguyen G, Burckle C, Sraer JD (2003) The renin receptor: the facts, the promise and the hope. Curr Opin Nephrol Hypertens 12:51–55

    Article  PubMed  CAS  Google Scholar 

  78. Nguyen G, Burckle CA, Sraer JD (2004) Renin/prorenin-receptor biochemistry and functional significance. Curr Hypertens Rep 6:129–132

    Article  PubMed  Google Scholar 

  79. Nguyen G, Delarue F, Burckle C, Bouzhir L, Giller T, Sraer JD (2002) Pivotal role of the renin/prorenin receptor in angiotensin II production and cellular responses to renin. J Clin Invest 109:1417–1427

    PubMed  CAS  Google Scholar 

  80. Nussberger J, Fluckiger JP, Hui KY, Evequoz D, Waeber B, Brunner HR (1991) Angiotensin I and II disappear completely from circulating blood within 48 hours after binephrectomy: improved measurement of angiotensins in rat plasma. J Hypertens Suppl 9:S230–S231

    PubMed  CAS  Google Scholar 

  81. Pech V, Kim YH, Weinstein AM, Everett LA, Pham TD, Wall SM (2007) Angiotensin II increases chloride absorption in the cortical collecting duct in mice through a pendrin-dependent mechanism. Am J Physiol Renal Physiol 292:F914–F920

    Article  PubMed  CAS  Google Scholar 

  82. Peters J, Farrenkopf R, Clausmeyer S, Zimmer J, Kantachuvesiri S, Sharp MG, Mullins JJ (2002) Functional significance of prorenin internalization in the rat heart. Circ Res 90:1135–1141

    Article  PubMed  CAS  Google Scholar 

  83. Peti-Peterdi J, Warnock DG, Bell PD (2002) Angiotensin II directly stimulates ENaC activity in the cortical collecting duct via AT(1) receptors. J Am Soc Nephrol 13:1131–1135

    Article  PubMed  CAS  Google Scholar 

  84. Ploth DW, Roy RN (1982) Renin-angiotensin influences on tubuloglomerular feedback activity in the rat. Kidney Int 22(Suppl 12):S114–S121

    Google Scholar 

  85. Pohl M, Kaminski H, Castrop H, Bader M, Himmerkus N, Bleich M, Bachmann S, Theilig F (2010) Intrarenal renin angiotensin system revisited: role of megalin-dependent endocytosis along the proximal nephron. J Biol Chem 285:41935–41946

    Article  PubMed  CAS  Google Scholar 

  86. Prescott G, Silversides DW, Reudelhuber TL (2002) Tissue activity of circulating prorenin. Am J Hypertens 15:280–285

    Article  PubMed  CAS  Google Scholar 

  87. Prieto MC, Gonzalez-Villalobos RA, Botros FT, Martin VL, Pagan J, Sato R, Lara LS, Feng Y, Fernandez F, Kobori H, Casarini DE, and Navar LG (2011) Reciprocal changes in renal ACE/Ang II and ACE2/Ang 1–7 are associated with enhanced collecting duct renin in Goldblatt hypertensive rats. Am J Physiol Renal Physiol 300, F749-F755. 1-5-2011.

    Google Scholar 

  88. Prieto MC, Williams DE, Liu L, Kavanagh KL, Mullins JJ, Mitchell KD (2010) Enhancement of renin and prorenin receptor in the collecting ducts of Cyp1a1-Ren2 rats contribute to development and progression of malignant hypertension. Am J Physiol Renal Physiol 300:F581–F588

    Article  PubMed  CAS  Google Scholar 

  89. Prieto-Carrasquero MC, Botros FT, Kobori H, Navar LG (2009) Collecting duct renin: a major player in angiotensin II-dependent hypertension. J Am Soc Hypertens 3:96–104

    Article  PubMed  Google Scholar 

  90. Prieto-Carrasquero MC, Botros FT, Pagan J, Kobori H, Seth DM, Casarini DE, Navar LG (2008) Collecting duct renin is upregulated in both kidneys of 2-kidney, 1-clip Goldblatt hypertensive rats. Hypertension 51:1590–1596

    Article  PubMed  CAS  Google Scholar 

  91. Prieto-Carrasquero MC, Harrison-Bernard LM, Kobori H, Ozawa Y, Hering-Smith KS, Hamm LL, Navar LG (2004) Enhancement of collecting duct renin in angiotensin II-dependent hypertensive rats. Hypertension 44:223–229

    Article  PubMed  CAS  Google Scholar 

  92. Prieto-Carrasquero MC, Kobori H, Ozawa Y, Gutierrez A, Seth D, Navar LG (2005) AT1 receptor-mediated enhancement of collecting duct renin in angiotensin II-dependent hypertensive rats. Am J Physiol Renal Physiol 289:F632–F637

    Article  PubMed  CAS  Google Scholar 

  93. Roffey J, Rosse C, Linch M, Hibbert A, McDonald NQ, Parker PJ (2009) Protein kinase C intervention: the state of play. Curr Opin Cell Biol 21:268–279

    Article  PubMed  CAS  Google Scholar 

  94. Rohrwasser A, Morgan T, Dillon HF, Zhao L, Callaway CW, Hillas E, Zhang S, Cheng T, Inagami T, Ward K, Terreros DA, Lalouel JM (1999) Elements of a paracrine tubular renin–angiotensin system along the entire nephron. Hypertension 34:1265–1274

    Article  PubMed  CAS  Google Scholar 

  95. Rosivall L, Taugner R (1986) The morphological basis of fluid balance in the interstitium of the juxtaglomerular apparatus. Cell Tissue Res 243:525–533

    Article  PubMed  CAS  Google Scholar 

  96. Sandberg MB, Riquier AD, Pihakaski-Maunsbach K, Mcdonough AA, Maunsbach AB (2007) ANG II provokes acute trafficking of distal tubule Na+-Cl(−) cotransporter to apical membrane. Am J Physiol Renal Physiol 293:F662–F669

    Article  PubMed  CAS  Google Scholar 

  97. Satofuka S, Ichihara A, Nagai N, Noda K, Ozawa Y, Fukamizu A, Tsubota K, Itoh H, Oike Y, Ishida S (2009) (Pro)renin receptor-mediated signal transduction and tissue renin–angiotensin system contribute to diabetes-induced retinal inflammation. Diabetes 58:1625–1633

    Article  PubMed  CAS  Google Scholar 

  98. Sealey JE, Laragh JH (1975) "Prorenin" in human plasma? Circ Res 36:10–16

    Article  PubMed  CAS  Google Scholar 

  99. Sun P, Yue P, Wang WH (2012) Angiotensin II stimulates epithelial sodium channels in the cortical collecting duct of the rat kidney. Am J Physiol Renal Physiol 302:F679–F687

    Article  PubMed  CAS  Google Scholar 

  100. Tank JE, Henrich WL, Moe OW (1997) Regulation of glomerular and proximal tubule renin mRNA by chronic changes in dietary NaCl. Am J Physiol Renal Physiol 273:F892–F898

    CAS  Google Scholar 

  101. Taugner R, Hackenthal E, Inagami T, Nobiling R, Poulsen K (1982) Vascular and tubular renin in the kidneys of mice. Histochemistry 75:473–484

    Article  PubMed  CAS  Google Scholar 

  102. Taugner R, Mannek E, Nobiling R, Buhrle CP, Hackenthal E, Ganten D, Inagami T, Schroder H (1984) Coexistence of renin and angiotensin II in epitheloid cell secretory granules of rat kidney. Histochemistry 81:39–45

    Article  PubMed  CAS  Google Scholar 

  103. Tipnis SR, Hooper NM, Hyde R, Karran E, Christie G, Turner AJ (2000) A human homolog of angiotensin-converting enzyme. Cloning and functional expression as a captopril-insensitive carboxypeptidase. J Biol Chem 275:33238–33243

    Article  PubMed  CAS  Google Scholar 

  104. van den Heuvel M, Batenburg WW, Jainandunsing S, Garrelds IM, van Gool JM, Feelders RA, van den Meiracker AH, Danser AH (2011) Urinary renin, but not angiotensinogen or aldosterone, reflects the renal renin–angiotensin–aldosterone system activity and the efficacy of renin–angiotensin–aldosterone system blockade in the kidney. J Hypertens 29:2147–2155

    Article  PubMed  CAS  Google Scholar 

  105. Verlander JW, Hassell KA, Royaux IE, Glapion DM, Wang ME, Everett LA, Green ED, Wall SM (2003) Deoxycorticosterone upregulates PDS (Slc26a4) in mouse kidney: role of pendrin in mineralocorticoid-induced hypertension. Hypertension 42:356–362

    Article  PubMed  CAS  Google Scholar 

  106. Verlander JW, Hong S, Pech V, Bailey JL, Agazatian D, Matthews SW, Coffman TM, Le T, Inagami T, Whitehill FM, Weiner ID, Farley DB, Kim YH, Wall SM (2011) Angiotensin II acts through the angiotensin 1a receptor to upregulate pendrin. Am J Physiol Renal Physiol 301:F1314–F1325

    Article  PubMed  CAS  Google Scholar 

  107. Von Thun AM, Vari RC, El-Dahr SS, Navar LG (1994) Augmentation of intrarenal angiotensin II levels by chronic angiotensin II infusion. Am J Physiol Renal Physiol 266:F120–F128

    Google Scholar 

  108. Wilcox CS, Dzau VJ (1992) Effect of captopril on the release of the components of the renin–angiotensin system into plasma and lymph. J Am Soc Nephrol 2:1241–1250

    PubMed  CAS  Google Scholar 

  109. Wilcox CS, Peart WS (1987) Release of renin and angiotensin II into plasma and lymph during hyperchloremia. Am J Physiol Renal Physiol 253:F734–F741

    CAS  Google Scholar 

  110. Yagil Y, Yagil C (2003) Hypothesis: ACE2 modulates blood pressure in the mammalian organism. Hypertension 41:871–873

    Article  PubMed  CAS  Google Scholar 

  111. Zhao D, Seth DM, Navar LG (2009) Enhanced distal nephron sodium reabsorption in chronic angiotensin II-infused mice. Hypertension 54:120–126

    Article  PubMed  CAS  Google Scholar 

  112. Zhuo JL, Imig JD, Hammond TG, Orengo S, Benes E, Navar LG (2002) Ang II accumulation in rat renal endosomes during Ang II-induced hypertension: role of AT(1) receptor. Hypertension 39:116–121

    Article  PubMed  CAS  Google Scholar 

  113. Zimmerman BG, Arendshorst WJ, DiBona GF, Hostetter TH, Ploth DW, Raij L (1986) Renal functional derangements in hypertension. Federation Proc 45(12):2661–2664

    CAS  Google Scholar 

  114. Zou L, Imig JD, Von Thun AM, Hymel A, Ono H, Navar LG (1996) Receptor-mediated intrarenal ANG II augmentation in ANG II-infused rats. Hypertension 28:669–677

    Article  PubMed  CAS  Google Scholar 

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Acknowledgments

The authors received support from the National Heart, Lung, and Blood Institute (HL-26371), the Institutional Award Program of the National Center for Research Resources, Centers of Biomedical Research Excellence (P20 RR-017659), and the American Heart Association (09BGIA2280440). We thank Debbie Olavarrieta for preparation of the manuscript.

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Authors and Affiliations

  1. Department of Physiology and Hypertension and Renal Center of Excellence, Tulane University School of Medicine, 1430 Tulane Avenue, New Orleans, LA, 70112, USA

    Minolfa C. Prieto, Alexis A. Gonzalez & L. Gabriel Navar

  2. Instituto de Química, Facultad de Ciencias, Pontificia Universidad Católica de Valparaíso, Valparaiso, Chile

    Alexis A. Gonzalez

  3. Department of Physiology, Tulane University Health Sciences Center, 1430 Tulane Avenue, New Orleans, LA, 70112, USA

    L. Gabriel Navar

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  1. Minolfa C. Prieto
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  2. Alexis A. Gonzalez
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  3. L. Gabriel Navar
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Correspondence to L. Gabriel Navar.

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This article is published as part of the special issue on the Renin–Angiotensin System.

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Prieto, M.C., Gonzalez, A.A. & Navar, L.G. Evolving concepts on regulation and function of renin in distal nephron. Pflugers Arch - Eur J Physiol 465, 121–132 (2013). https://doi.org/10.1007/s00424-012-1151-6

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  • DOI: https://doi.org/10.1007/s00424-012-1151-6

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