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Intrarenal Angiotensin-Converting Enzyme: the Old and the New

  • Therapeutic Trials (M Weir, Section Editor)
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Abstract

Purpose of Review

The intrarenal renin-angiotensin-aldosterone system (RAS) is an independent paracrine hormonal system with an increasingly prominent role in hypertension and renal disease. Two enzyme components of this system are angiotensin-converting enzyme (ACE) and more recently discovered ACE2. The purpose of this review is to describe recent discoveries regarding the roles of intrarenal ACE and ACE2 and their interaction.

Recent Findings

Renal tubular ACE contributes to salt-sensitive hypertension. Additionally, the relative expression and activity of intrarenal ACE and ACE2 are central to promoting or inhibiting different renal pathologies including renovascular hypertension, diabetic nephropathy, and renal fibrosis.

Summary

Renal ACE and ACE2 represent two opposing axes within the intrarenal RAS system whose interaction determines the progression of several common disease processes. While this relationship remains complex and incompletely understood, further investigations hold the potential for creating novel approaches to treating hypertension and kidney disease.

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References

Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance

  1. Rohrwasser A, Morgan T, Dillon HF, Zhao L, Callaway CW, Hillas E, et al. Elements of a paracrine tubular renin-angiotensin system along the entire nephron. Hypertension. 1999;34:1265–74.

    Article  CAS  PubMed  Google Scholar 

  2. • Yang T, Xu C. Physiology and pathophysiology of the intrarenal renin-angiotensin system: an update. J Am Soc Nephrol. 2017;28:1040–9. https://doi.org/10.1681/ASN.2016070734. A recent review on the function and regulation of the intrarenal RAS in contrast with systemic RAS.

    Article  PubMed  Google Scholar 

  3. Matsusaka T, Niimura F, Shimizu A, Pastan I, Saito A, Kobori H, et al. Liver angiotensinogen is the primary source of renal angiotensin II. J Am Soc Nephrol. 2012;23:1181–9. https://doi.org/10.1681/ASN.2011121159.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. Casarini DE, Boim MA, Stella RC, Krieger-Azzolini MH, Krieger JE, Schor N. Angiotensin I-converting enzyme activity in tubular fluid along the rat nephron. Am J Phys. 1997;272:F405–9.

    CAS  Google Scholar 

  5. Nishiyama A, Seth DM, Navar LG. Renal interstitial fluid angiotensin I and angiotensin II concentrations during local angiotensin-converting enzyme inhibition. J Am Soc Nephrol. 2002;13:2207–12.

    Article  CAS  PubMed  Google Scholar 

  6. • Carey RM. The intrarenal renin-angiotensin system in hypertension. Adv Chronic Kidney Dis. 2015;22:204–10. https://doi.org/10.1053/j.ackd.2014.11.004. A review of recent advances in understanding of the intrarenal RAS as well as the role of newer RAS pathways in hypertension.

    Article  PubMed  Google Scholar 

  7. Carey RM, Siragy HM. Newly recognized components of the renin-angiotensin system: potential roles in cardiovascular and renal regulation. Endocr Rev. 2003;24:261–71. https://doi.org/10.1210/er.2003-0001.

    Article  CAS  PubMed  Google Scholar 

  8. Erdos EG, Skidgel RA. Structure and functions of human angiotensin I converting enzyme (kininase II). Biochem Soc Trans. 1985;13:42–4.

    Article  CAS  PubMed  Google Scholar 

  9. Sachetelli S, Liu Q, Zhang SL, Liu F, Hsieh TJ, Brezniceanu ML, et al. RAS blockade decreases blood pressure and proteinuria in transgenic mice overexpressing rat angiotensinogen gene in the kidney. Kidney Int. 2006;69:1016–23.

    Article  CAS  PubMed  Google Scholar 

  10. Crowley SD, Gurley SB, Herrera MJ, Ruiz P, Griffiths R, Kumar AP, et al. Angiotensin II causes hypertension and cardiac hypertrophy through its receptors in the kidney. Proc Natl Acad Sci U S A. 2006;103:17985–90.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. • Giani JF, Shah KH, Khan Z, Bernstein EA, Shen XZ, McDonough AA, et al. The intrarenal generation of angiotensin II is required for experimental hypertension. Curr Opin Pharmacol. 2015;21:73–81. https://doi.org/10.1016/j.coph.2015.01.002. This study shows that mice lacking renal ACE fail to generate intrarenal Ang II or develop hypertension when treated with Ang II or L-NAME.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Rahimi Z. The role of renin angiotensin aldosterone system genes in diabetic nephropathy. Can J Diabetes. 2016;40:178–83. https://doi.org/10.1016/j.jcjd.2015.08.016.

    Article  PubMed  Google Scholar 

  13. Bernstein KE, Giani JF, Shen XZ, Gonzalez-Villalobos RA. Renal angiotensin-converting enzyme and blood pressure control. Curr Opin Nephrol Hypertens. 2014;23:106–12. https://doi.org/10.1097/01.mnh.0000441047.13912.56.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Gonzalez-Villalobos RA, Billet S, Kim C, Satou R, Fuchs S, Bernstein KE, et al. Intrarenal angiotensin-converting enzyme induces hypertension in response to angiotensin I infusion. J Am Soc Nephrol. 2011;22:449–59. https://doi.org/10.1681/ASN.2010060624.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. •• Giani JF, Eriguchi M, Bernstein EA, Katsumata M, Shen XZ, Li L, et al. Renal tubular angiotensin converting enzyme is responsible for nitro-L-arginine methyl ester (L-NAME)-induced salt sensitivity. Kidney Int. 2017;91:856–67. This study uses a mouse model with no renal tubular ACE and another with ACE only in the renal tubular epithelium to demonstrate that renal tubular ACE is critical for development of salt sensitivity in response to L-NAME.

    Article  CAS  PubMed  Google Scholar 

  16. Liebau MC, Lang D, Bohm J, Endlich N, Bek MJ, Witherden I, et al. Functional expression of the renin-angiotensin system in human podocytes. Am J Physiol Renal Physiol. 2006;290:F710–9.

    Article  CAS  PubMed  Google Scholar 

  17. Gonzalez-Villalobos RA, Satou R, Ohashi N, Semprun-Prieto LC, Katsurada A, Kim C, et al. Intrarenal mouse renin-angiotensin system during ANG II-induced hypertension and ACE inhibition. Am J Physiol Renal Physiol. 2010;298:F150–7. https://doi.org/10.1152/ajprenal.00477.2009.

    Article  CAS  PubMed  Google Scholar 

  18. Vio CP, Jeanneret VA. Local induction of angiotensin-converting enzyme in the kidney as a mechanism of progressive renal diseases. Kidney Int Suppl. 2003;86:S57–63.

    Article  CAS  Google Scholar 

  19. Donoghue M, Hsieh F, Baronas E, Godbout K, Gosselin M, Stagliano N, et al. A novel angiotensin-converting enzyme-related carboxypeptidase (ACE2) converts angiotensin I to angiotensin 1-9. Circ Res. 2000;87:E1–9.

    Article  CAS  PubMed  Google Scholar 

  20. Padda RS, Shi Y, Lo CS, Zhang SL, Chan JS. Angiotensin-(1–7): a novel peptide to treat hypertension and nephropathy in diabetes? J Diabetes Metab. 2015;6. doi: https://doi.org/10.4172/2155-6156.1000615.

  21. Shi Y, Lo CS, Padda R, Abdo S, Chenier I, Filep JG, et al. Angiotensin-(1-7) prevents systemic hypertension, attenuates oxidative stress and tubulointerstitial fibrosis, and normalizes renal angiotensin-converting enzyme 2 and Mas receptor expression in diabetic mice. Clin Sci (Lond). 2015;128:649–63. https://doi.org/10.1042/CS20140329.

    Article  CAS  Google Scholar 

  22. Xiao F, Burns KD. Measurement of angiotensin converting enzyme 2 activity in biological fluid (ACE2). Methods Mol Biol. 2017;1527:101–15. https://doi.org/10.1007/978-1-4939-6625-7_8.

    Article  PubMed  Google Scholar 

  23. Lely AT, Hamming I, van Goor H, Navis GJ. Renal ACE2 expression in human kidney disease. J Pathol. 2004;204:587–93. https://doi.org/10.1002/path.1670.

    Article  CAS  PubMed  Google Scholar 

  24. Kuba K, Imai Y, Rao S, Gao H, Guo F, Guan B, et al. A crucial role of angiotensin converting enzyme 2 (ACE2) in SARS coronavirus-induced lung injury. Nat Med. 2005;11:875–9.

    Article  CAS  PubMed  Google Scholar 

  25. Osterreicher CH, Taura K, De Minicis S, Seki E, Penz-Osterreicher M, Kodama Y, et al. Angiotensin-converting-enzyme 2 inhibits liver fibrosis in mice. Hepatology. 2009;50:929–38. https://doi.org/10.1002/hep.23104.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. Liu CX, Hu Q, Wang Y, Zhang W, Ma ZY, Feng JB, et al. Angiotensin-converting enzyme (ACE) 2 overexpression ameliorates glomerular injury in a rat model of diabetic nephropathy: a comparison with ACE inhibition. Mol Med. 2011;17:59–69. https://doi.org/10.2119/molmed.2010.00111.

    Article  PubMed  Google Scholar 

  27. • Callera GE, Antunes TT, Correa JW, Moorman D, Gutsol A, He Y, et al. Differential renal effects of candesartan at high and ultra-high doses in diabetic mice-potential role of the ACE2/AT2R/Mas axis. Biosci Rep. 2016;36:e00398. This study demonstrates that the renoprotective effects of the Candesartan occur with upregulation of the ACE2/AT2R/Mas axis.

    Article  PubMed  PubMed Central  Google Scholar 

  28. • Huang YF, Zhang Y, Liu CX, Huang J, Ding GH. microRNA-125b contributes to high glucose-induced reactive oxygen species generation and apoptosis in HK-2 renal tubular epithelial cells by targeting angiotensin-converting enzyme 2. Eur Rev Med Pharmacol Sci. 2016;20:4055–62. This in vitro study shows that blocking microRNA-125b mediated downregulation of ACE2 in renal tubular epithelial cells and prevents high glucose-mediated ROS production and apoptosis.

    PubMed  Google Scholar 

  29. • Berger RC, Vassallo PF, Crajoinas Rde O, Oliveira ML, Martins FL, Nogueira BV, et al. Renal effects and underlying molecular mechanisms of long-term salt content diets in spontaneously hypertensive rats. PLoS One. 2015;10:e0141288. https://doi.org/10.1371/journal.pone.0141288. This study describes the effects of high- and low-salt diets on ACE/ACE2 ratio and associated renal injury.

    Article  PubMed  PubMed Central  Google Scholar 

  30. Chan J, Lo CS, Shi Y, Chenier I, Zhang SL. Os 25-03 overexpression of heterogeneous nuclear ribonucleoprotein F prevents systemic hypertension and kidney injury and normalizes renal renin-angiotensin system genes expression in type 2 diabetic Db/db transgenic mice. J Hypertens. 2016;34(Suppl 1 - ISH 2016 Abstract Book):e245. https://doi.org/10.1097/01.hjh.0000500552.89974.b8.

    Article  Google Scholar 

  31. Bae EH, Konvalinka A, Fang F, Zhou X, Williams V, Maksimowski N, et al. Characterization of the intrarenal renin-angiotensin system in experimental Alport syndrome. Am J Pathol. 2015;185:1423–35. https://doi.org/10.1016/j.ajpath.2015.01.021.

    Article  CAS  PubMed  Google Scholar 

  32. Ross MJ, Nangaku M. ACE2 as therapy for glomerular disease: the devil is in the detail. Kidney Int. 2017;91:1269–71.

    Article  CAS  PubMed  Google Scholar 

  33. • Chen LJ, Xu YL, Song B, Yu HM, Oudit GY, Xu R, et al. Angiotensin-converting enzyme 2 ameliorates renal fibrosis by blocking the activation of mTOR/ERK signaling in apolipoprotein E-deficient mice. Peptides. 2016;79:49–57. https://doi.org/10.1016/j.peptides.2016.03.008. This study demonstrates that recombinant ACE2 prevents Ang II-mediated fibrosis in ApoE knockout mice via upregulation Ang(1–7) and inhibition of mTOR/ERK.

    Article  CAS  PubMed  Google Scholar 

  34. • Le Y, Zheng Z, Xue J, Cheng M, Guan M, Xue Y. Effects of exendin-4 on the intrarenal renin-angiotensin system and interstitial fibrosis in unilateral ureteral obstruction mice: exendin-4 and unilateral ureteral obstruction. J Renin-Angiotensin-Aldosterone Syst. 2016;17:1470320316677918. This study demonstrates that exendin-4 reduces renal fibrosis in the setting of ureteral obstruction while increasing ACE2 and decreasing ACE expressions.

    Article  PubMed  Google Scholar 

  35. Rodriguez-Iturbe B, Franco M, Johnson RJ. Impaired pressure natriuresis is associated with interstitial inflammation in salt-sensitive hypertension. Curr Opin Nephrol Hypertens. 2013;22:37–44. https://doi.org/10.1097/MNH.0b013e32835b3d54.

    Article  PubMed  Google Scholar 

  36. •• Giani JF, Bernstein KE, Janjulia T, Han J, Toblli JE, Shen XZ, et al. Salt sensitivity in response to renal injury requires renal angiotensin-converting enzyme. Hypertension. 2015;66:534–42. https://doi.org/10.1161/HYPERTENSIONAHA.115.05320. This study demonstrates that mice lacking renal ACE fail to develop salt sensitivity following treatment with L-NAME due to reduced intrarenal Ang II production and alterations in renal sodium channel activity.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  37. Gonzalez-Villalobos RA, Janjoulia T, Fletcher NK, Giani JF, Nguyen MT, Riquier-Brison AD, et al. The absence of intrarenal ACE protects against hypertension. J Clin Invest. 2013;123:2011–23. https://doi.org/10.1172/JCI65460.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  38. Giani JF, Janjulia T, Kamat N, Seth DM, Blackwell WL, Shah KH, et al. Renal angiotensin-converting enzyme is essential for the hypertension induced by nitric oxide synthesis inhibition. J Am Soc Nephrol. 2014;25:2752–63. https://doi.org/10.1681/ASN.2013091030.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  39. Klimas J, Olvedy M, Ochodnicka-Mackovicova K, Kruzliak P, Cacanyiova S, Kristek F, et al. Perinatally administered losartan augments renal ACE2 expression but not cardiac or renal Mas receptor in spontaneously hypertensive rats. J Cell Mol Med. 2015;19:1965–74. https://doi.org/10.1111/jcmm.12573.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  40. Huskova Z, Kopkan L, Cervenkova L, Dolezelova S, Vanourkova Z, Skaroupkova P, et al. Intrarenal alterations of the angiotensin-converting enzyme type 2/angiotensin 1-7 complex of the renin-angiotensin system do not alter the course of malignant hypertension in Cyp1a1-Ren-2 transgenic rats. Clin Exp Pharmacol Physiol. 2016;43:438–49. https://doi.org/10.1111/1440-1681.12553.

    Article  CAS  PubMed  Google Scholar 

  41. • Kim YG, Lee SH, Kim SY, Lee A, Moon JY, Jeong KH, et al. Sequential activation of the intrarenal renin-angiotensin system in the progression of hypertensive nephropathy in Goldblatt rats. Am J Physiol Renal Physiol. 2016:311, F195–F206. https://doi.org/10.1152/ajprenal.00001.2015. This study describes the temporal changes in ACE and ACE2 expression in the 2K1C model and hypothesizes their relative contribution to the generation and maintenance of hypertension.

  42. •• Chu PL, Gigliotti JC, Cechova S, Bodonyi-Kovacs G, Chan F, Ralph DL, et al. Renal collectrin protects against salt-sensitive hypertension and is downregulated by angiotensin II. J Am Soc Nephrol. 2017;28:1826–37. https://doi.org/10.1681/ASN.2016060675. This study demonstrates through cross-transplantation of collectrin knockout kidneys into wild-type mice that collectrin protects against salt-sensitive hypertension via downregulation of the NHE3 sodium transporter.

    Article  PubMed  Google Scholar 

  43. Cechova S, Zeng Q, Billaud M, Mutchler S, Rudy CK, Straub AC, et al. Loss of collectrin, an angiotensin-converting enzyme 2 homolog, uncouples endothelial nitric oxide synthase and causes hypertension and vascular dysfunction. Circulation. 2013;128:1770–80. https://doi.org/10.1161/CIRCULATIONAHA.113.003301.

    Article  CAS  PubMed  Google Scholar 

  44. Ye M, Wysocki J, William J, Soler MJ, Cokic I, Batlle D. Glomerular localization and expression of angiotensin-converting enzyme 2 and angiotensin-converting enzyme: implications for albuminuria in diabetes. J Am Soc Nephrol. 2006;17:3067–75.

    Article  CAS  PubMed  Google Scholar 

  45. Soler MJ, Wysocki J, Ye M, Lloveras J, Kanwar Y, Batlle D. ACE2 inhibition worsens glomerular injury in association with increased ACE expression in streptozotocin-induced diabetic mice. Kidney Int. 2007;72:614–23.

    Article  CAS  PubMed  Google Scholar 

  46. Shiota A, Yamamoto K, Ohishi M, Tatara Y, Ohnishi M, Maekawa Y, et al. Loss of ACE2 accelerates time-dependent glomerular and tubulointerstitial damage in streptozotocin-induced diabetic mice. Hypertens Res. 2010;33:298–307. https://doi.org/10.1038/hr.2009.231.

    Article  PubMed  Google Scholar 

  47. Clotet S, Soler MJ, Rebull M, Gimeno J, Gurley SB, Pascual J, et al. Gonadectomy prevents the increase in blood pressure and glomerular injury in angiotensin-converting enzyme 2 knockout diabetic male mice. Effects on renin-angiotensin system. J Hypertens. 2016;34:1752–65. https://doi.org/10.1097/HJH.0000000000001015.

    Article  CAS  PubMed  Google Scholar 

  48. •• Wysocki J, Ye M, Khattab AM, Fogo A, Martin A, David NV, et al. Angiotensin-converting enzyme 2 amplification limited to the circulation does not protect mice from development of diabetic nephropathy. Kidney Int. 2017;91:1336–46. This study finds that increasing systemic ACE2 with recombinant ACE2 does not prevent diabetic changes in GFR, albuminuria, or glomerular histopathology.

    Article  CAS  PubMed  Google Scholar 

  49. Xiao F, Zimpelmann J, Agaybi S, Gurley SB, Puente L, Burns KD. Characterization of angiotensin-converting enzyme 2 ectodomain shedding from mouse proximal tubular cells. PLoS One. 2014;9:e85958. https://doi.org/10.1371/journal.pone.0085958.

    Article  PubMed  PubMed Central  Google Scholar 

  50. Xiao F, Zimpelmann J, Burger D, Kennedy C, Hebert RL, Burns KD. Protein kinase C-delta mediates shedding of angiotensin-converting enzyme 2 from proximal tubular cells. Front Pharmacol. 2016;7:146. https://doi.org/10.3389/fphar.2016.00146.

    Article  PubMed  PubMed Central  Google Scholar 

  51. • Liang Y, Deng H, Bi S, Cui Z, A L, Zheng D, et al. Urinary angiotensin converting enzyme 2 increases in patients with type 2 diabetic mellitus. Kidney Blood Press Res. 2015;40:101–10. https://doi.org/10.1159/000368486. This study demonstrates a correlation between urinary ACE2 to creatinine ratio and various measures metabolic markers of disease including hemoglobin A1C, cholesterol, and blood glucose.

    Article  CAS  PubMed  Google Scholar 

  52. Mariana CP, Ramona PA, Ioana BC, Diana M, Claudia RC, Stefan VD, et al. Urinary angiotensin converting enzyme 2 is strongly related to urinary nephrin in type 2 diabetes patients. Int Urol Nephrol. 2016;48:1491–7. https://doi.org/10.1007/s11255-016-1334-8.

    Article  CAS  PubMed  Google Scholar 

  53. Riera M, Anguiano L, Clotet S, Roca-Ho H, Rebull M, Pascual J, et al. Paricalcitol modulates ACE2 shedding and renal ADAM17 in NOD mice beyond proteinuria. Am J Physiol Renal Physiol. 2016;310:F534–46. https://doi.org/10.1152/ajprenal.00082.2015.

    Article  CAS  PubMed  Google Scholar 

  54. • Lin M, Gao P, Zhao T, He L, Li M, Li Y, et al. Calcitriol regulates angiotensin-converting enzyme and angiotensin converting-enzyme 2 in diabetic kidney disease. Mol Biol Rep. 2016;43:397–406. https://doi.org/10.1007/s11033-016-3971-5. This study demonstrates that calcitriol reduces the renal ACE to ACE2 ratio in diabetic rats with reduction in proteinuria.

    Article  CAS  PubMed  Google Scholar 

  55. Oudit GY, Liu GC, Zhong J, Basu R, Chow FL, Zhou J, et al. Human recombinant ACE2 reduces the progression of diabetic nephropathy. Diabetes. 2010;59:529–38. https://doi.org/10.2337/db09-1218.

    Article  CAS  PubMed  Google Scholar 

  56. Jin HY, Chen LJ, Zhang ZZ, Xu YL, Song B, Xu R, et al. Deletion of angiotensin-converting enzyme 2 exacerbates renal inflammation and injury in apolipoprotein E-deficient mice through modulation of the nephrin and TNF-alpha-TNFRSF1A signaling. J Transl Med. 2015;13:255. https://doi.org/10.1186/s12967-015-0616-8.

    Article  PubMed  PubMed Central  Google Scholar 

  57. • Zheng Y, Tang L, Huang W, Yan R, Ren F, Luo L, et al. Anti-inflammatory effects of Ang-(1-7) in ameliorating HFD-induced renal injury through LDLr-SREBP2-SCAP pathway. PLoS One. 2015;10:e0136187. https://doi.org/10.1371/journal.pone.0136187. This study demonstrates that administration of Ang(1–7) reduces lipid-induced renal injury, inflammation, and lipid deposition through the LDL receptor, SREBP-2, and SCAP pathway.

    Article  PubMed  PubMed Central  Google Scholar 

  58. Velkoska E, Patel SK, Griggs K, Pickering RJ, Tikellis C, Burrell LM. Short-term treatment with diminazene aceturate ameliorates the reduction in kidney ACE2 activity in rats with subtotal nephrectomy. PLoS One. 2015;10:e0118758. https://doi.org/10.1371/journal.pone.0118758.

    Article  PubMed  PubMed Central  Google Scholar 

  59. Anguiano L, Riera M, Pascual J, Valdivielso JM, Barrios C, Betriu A, et al. NEFRONA study. Circulating angiotensin-converting enzyme 2 activity in patients with chronic kidney disease without previous history of cardiovascular disease. Nephrol Dial Transplant. 2015;30:1176–85. https://doi.org/10.1093/ndt/gfv025.

    Article  CAS  PubMed  Google Scholar 

  60. Abe M, Maruyama N, Oikawa O, Maruyama T, Okada K, Soma M. Urinary ACE2 is associated with urinary L-FABP and albuminuria in patients with chronic kidney disease. Scand J Clin Lab Invest. 2015;75:421–7. https://doi.org/10.3109/00365513.2015.1054871.

    Article  CAS  PubMed  Google Scholar 

  61. Bae EH, Fang F, Williams VR, Konvalinka A, Zhou X, Patel VB, et al. Murine recombinant angiotensin-converting enzyme 2 attenuates kidney injury in experimental Alport syndrome. Kidney Int. 2017;91:1347–61.

    Article  CAS  PubMed  Google Scholar 

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  1. Division of Endocrinology and Metabolism, Department of Medicine, University of Virginia Health System, P.O. Box 801409, Charlottesville, VA, 22908-1409, USA

    Silas Culver, Caixia Li & Helmy M. Siragy

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  1. Silas Culver
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All authors contributed to the manuscript writing. The authors have read and approved the final version of the manuscript.

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Correspondence to Helmy M. Siragy.

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Culver, S., Li, C. & Siragy, H.M. Intrarenal Angiotensin-Converting Enzyme: the Old and the New. Curr Hypertens Rep 19, 80 (2017). https://doi.org/10.1007/s11906-017-0778-2

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