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Erschienen in: Current Hypertension Reports 4/2015

01.04.2015 | Hypertension and the Kidney (RM Carey, Section Editor)

Relative Roles of Principal and Intercalated Cells in the Regulation of Sodium Balance and Blood Pressure

verfasst von: Régine Chambrey, Francesco Trepiccione

Erschienen in: Current Hypertension Reports | Ausgabe 4/2015

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Abstract

The kidney continuously adapts daily renal excretion of NaCl to match dietary intakes in order to maintain the NaCl content of the body, and keep vascular volume constant. Any situation that leads to NaCl retention favors a rise in blood pressure. The aldosterone-sensitive distal nephron, which contains two main types of cells, principal (PC) and intercalated (IC) cells, is an important site for the final regulation of urinary Na+ excretion. Research over the past 20 years established a paradigm in which PCs are the exclusive site of Na+ absorption while ICs are solely dedicated to acid-base transport. Recent studies have revealed the unexpected importance of ICs for NaCl reabsorption. Here, we review the mechanisms of Na+ and Cl transport in the aldosterone-sensitive distal nephron, with emphasis on the role of ICs in maintaining NaCl balance and normal blood pressure.
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Zurück zum Zitat Wildman SS, Boone M, Peppiatt-Wildman CM, Contreras-Sanz A, King BF, Shirley DG, et al. Nucleotides downregulate aquaporin 2 via activation of apical P2 receptors. J Am Soc Nephrol. 2009;20(7):1480–90.PubMedCentralPubMed Wildman SS, Boone M, Peppiatt-Wildman CM, Contreras-Sanz A, King BF, Shirley DG, et al. Nucleotides downregulate aquaporin 2 via activation of apical P2 receptors. J Am Soc Nephrol. 2009;20(7):1480–90.PubMedCentralPubMed
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Zurück zum Zitat Rieg T, Bundey RA, Chen Y, Deschenes G, Junger W, Insel PA, et al. Mice lacking P2Y2 receptors have salt-resistant hypertension and facilitated renal Na+ and water reabsorption. FASEB J. 2007;21(13):3717–26. Rieg T, Bundey RA, Chen Y, Deschenes G, Junger W, Insel PA, et al. Mice lacking P2Y2 receptors have salt-resistant hypertension and facilitated renal Na+ and water reabsorption. FASEB J. 2007;21(13):3717–26.
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Zurück zum Zitat Terada Y, Knepper MA. Thiazide-sensitive NaCl absorption in rat cortical collecting duct. Am J Physiol. 1990;259(3 Pt 2):F519–28.PubMed Terada Y, Knepper MA. Thiazide-sensitive NaCl absorption in rat cortical collecting duct. Am J Physiol. 1990;259(3 Pt 2):F519–28.PubMed
61.••
Zurück zum Zitat Leviel F, Hubner CA, Houillier P, Morla L, El Moghrabi S, Brideau G, et al. The Na + -dependent chloride-bicarbonate exchanger SLC4A8 mediates an electroneutral Na + reabsorption process in the renal cortical collecting ducts of mice. J Clin Invest. 2010;120(5):1627–35. This study demonstrates the presence of electroneutral, amiloride resistant, thiazide- sensitive transepithelial NaCl absorption in mouse CCDs.PubMedCentralPubMed Leviel F, Hubner CA, Houillier P, Morla L, El Moghrabi S, Brideau G, et al. The Na + -dependent chloride-bicarbonate exchanger SLC4A8 mediates an electroneutral Na + reabsorption process in the renal cortical collecting ducts of mice. J Clin Invest. 2010;120(5):1627–35. This study demonstrates the presence of electroneutral, amiloride resistant, thiazide- sensitive transepithelial NaCl absorption in mouse CCDs.PubMedCentralPubMed
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Zurück zum Zitat Amasheh S, Milatz S, Krug SM, Bergs M, Amasheh M, Schulzke JD, et al. Na + absorption defends from paracellular back-leakage by claudin-8 upregulation. Biochem Biophys Res Commun. 2009;378(1):45–50.PubMed Amasheh S, Milatz S, Krug SM, Bergs M, Amasheh M, Schulzke JD, et al. Na + absorption defends from paracellular back-leakage by claudin-8 upregulation. Biochem Biophys Res Commun. 2009;378(1):45–50.PubMed
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Zurück zum Zitat Le Moellic C, Boulkroun S, Gonzalez-Nunez D, Dublineau I, Cluzeaud F, Fay M, et al. Aldosterone and tight junctions: modulation of claudin-4 phosphorylation in renal collecting duct cells. Am J Physiol Cell Physiol. 2005;289(6):C1513–21.PubMed Le Moellic C, Boulkroun S, Gonzalez-Nunez D, Dublineau I, Cluzeaud F, Fay M, et al. Aldosterone and tight junctions: modulation of claudin-4 phosphorylation in renal collecting duct cells. Am J Physiol Cell Physiol. 2005;289(6):C1513–21.PubMed
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Zurück zum Zitat Sansom SC, O’Neil RG. Mineralocorticoid regulation of apical cell membrane Na + and K+ transport of the cortical collecting duct. Am J Physiol. 1985;248(6 Pt 2):F858–68.PubMed Sansom SC, O’Neil RG. Mineralocorticoid regulation of apical cell membrane Na + and K+ transport of the cortical collecting duct. Am J Physiol. 1985;248(6 Pt 2):F858–68.PubMed
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Zurück zum Zitat Hou J, Renigunta A, Yang J, Waldegger S. Claudin-4 forms paracellular chloride channel in the kidney and requires claudin-8 for tight junction localization. Proc Natl Acad Sci U S A. 2010;107(42):18010–5.PubMedCentralPubMed Hou J, Renigunta A, Yang J, Waldegger S. Claudin-4 forms paracellular chloride channel in the kidney and requires claudin-8 for tight junction localization. Proc Natl Acad Sci U S A. 2010;107(42):18010–5.PubMedCentralPubMed
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Zurück zum Zitat Yamauchi K, Rai T, Kobayashi K, Sohara E, Suzuki T, Itoh T, et al. Disease-causing mutant WNK4 increases paracellular chloride permeability and phosphorylates claudins. Proc Natl Acad Sci U S A. 2004;101(13):4690–4.PubMedCentralPubMed Yamauchi K, Rai T, Kobayashi K, Sohara E, Suzuki T, Itoh T, et al. Disease-causing mutant WNK4 increases paracellular chloride permeability and phosphorylates claudins. Proc Natl Acad Sci U S A. 2004;101(13):4690–4.PubMedCentralPubMed
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Zurück zum Zitat Schambelan M, Sebastian A, Rector Jr FC. Mineralocorticoid-resistant renal hyperkalemia without salt wasting (type II pseudohypoaldosteronism): role of increased renal chloride reabsorption. Kidney Int. 1981;19(5):716–27.PubMed Schambelan M, Sebastian A, Rector Jr FC. Mineralocorticoid-resistant renal hyperkalemia without salt wasting (type II pseudohypoaldosteronism): role of increased renal chloride reabsorption. Kidney Int. 1981;19(5):716–27.PubMed
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Zurück zum Zitat Take C, Ikeda K, Kurasawa T, Kurokawa K. Increased chloride reabsorption as an inherited renal tubular defect in familial type II pseudohypoaldosteronism. N Engl J Med. 1991;324(7):472–6.PubMed Take C, Ikeda K, Kurasawa T, Kurokawa K. Increased chloride reabsorption as an inherited renal tubular defect in familial type II pseudohypoaldosteronism. N Engl J Med. 1991;324(7):472–6.PubMed
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Zurück zum Zitat Kahle KT, Rinehart J, Ring A, Gimenez I, Gamba G, Hebert SC, et al. WNK protein kinases modulate cellular Cl- flux by altering the phosphorylation state of the Na-K-Cl and K-Cl cotransporters. Physiology (Bethesda). 2006;21:326–35. Kahle KT, Rinehart J, Ring A, Gimenez I, Gamba G, Hebert SC, et al. WNK protein kinases modulate cellular Cl- flux by altering the phosphorylation state of the Na-K-Cl and K-Cl cotransporters. Physiology (Bethesda). 2006;21:326–35.
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Zurück zum Zitat Gong Y, Yu M, Yang J, Gonzales E, Perez R, Hou M, et al. The Cap1-claudin-4 regulatory pathway is important for renal chloride reabsorption and blood pressure regulation. Proc Natl Acad Sci U S A. 2014;111(36):E3766–74.PubMedCentralPubMed Gong Y, Yu M, Yang J, Gonzales E, Perez R, Hou M, et al. The Cap1-claudin-4 regulatory pathway is important for renal chloride reabsorption and blood pressure regulation. Proc Natl Acad Sci U S A. 2014;111(36):E3766–74.PubMedCentralPubMed
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Zurück zum Zitat Wall SM, Hassell KA, Royaux IE, Green ED, Chang JY, Shipley GL, et al. Localization of pendrin in mouse kidney. Am J Physiol Ren Physiol. 2003;284(1):F229–41. Wall SM, Hassell KA, Royaux IE, Green ED, Chang JY, Shipley GL, et al. Localization of pendrin in mouse kidney. Am J Physiol Ren Physiol. 2003;284(1):F229–41.
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Zurück zum Zitat Kim YH, Kwon TH, Frische S, Kim J, Tisher CC, Madsen KM, et al. Immunocytochemical localization of pendrin in intercalated cell subtypes in rat and mouse kidney. Am J Physiol Ren Physiol. 2002;283(4):F744–54. Kim YH, Kwon TH, Frische S, Kim J, Tisher CC, Madsen KM, et al. Immunocytochemical localization of pendrin in intercalated cell subtypes in rat and mouse kidney. Am J Physiol Ren Physiol. 2002;283(4):F744–54.
73.•
Zurück zum Zitat Royaux IE, Wall SM, Karniski LP, Everett LA, Suzuki K, Knepper MA, et al. Pendrin, encoded by the Pendred syndrome gene, resides in the apical region of renal intercalated cells and mediates bicarbonate secretion. Proc Natl Acad Sci U S A. 2001;98(7):4221–6. This study identified the apical Cl−/HCO3− exchanger of β- intercalated cells as the pendrin gene product.PubMedCentralPubMed Royaux IE, Wall SM, Karniski LP, Everett LA, Suzuki K, Knepper MA, et al. Pendrin, encoded by the Pendred syndrome gene, resides in the apical region of renal intercalated cells and mediates bicarbonate secretion. Proc Natl Acad Sci U S A. 2001;98(7):4221–6. This study identified the apical Cl−/HCO3− exchanger of β- intercalated cells as the pendrin gene product.PubMedCentralPubMed
74.•
Zurück zum Zitat Verlander JW, Hassell KA, Royaux IE, Glapion DM, Wang ME, Everett LA, et al. Deoxycorticosterone upregulates PDS (Slc26a4) in mouse kidney: role of pendrin in mineralocorticoid-induced hypertension. Hypertension. 2003;42(3):356–62. This study demonstrated that pendrin is critical in the pathogenesis of mineralocorticoid-induced hypertension.PubMed Verlander JW, Hassell KA, Royaux IE, Glapion DM, Wang ME, Everett LA, et al. Deoxycorticosterone upregulates PDS (Slc26a4) in mouse kidney: role of pendrin in mineralocorticoid-induced hypertension. Hypertension. 2003;42(3):356–62. This study demonstrated that pendrin is critical in the pathogenesis of mineralocorticoid-induced hypertension.PubMed
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Zurück zum Zitat Kim YH, Pech V, Spencer KB, Beierwaltes WH, Everett LA, Green ED, et al. Reduced ENaC protein abundance contributes to the lower blood pressure observed in pendrin-null mice. Am J Physiol Ren Physiol. 2007;293(4):F1314–24. Kim YH, Pech V, Spencer KB, Beierwaltes WH, Everett LA, Green ED, et al. Reduced ENaC protein abundance contributes to the lower blood pressure observed in pendrin-null mice. Am J Physiol Ren Physiol. 2007;293(4):F1314–24.
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Zurück zum Zitat Wall SM, Kim YH, Stanley L, Glapion DM, Everett LA, Green ED, et al. NaCl restriction upregulates renal Slc26a4 through subcellular redistribution: role in Cl- conservation. Hypertension. 2004;44(6):982–7.PubMed Wall SM, Kim YH, Stanley L, Glapion DM, Everett LA, Green ED, et al. NaCl restriction upregulates renal Slc26a4 through subcellular redistribution: role in Cl- conservation. Hypertension. 2004;44(6):982–7.PubMed
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Zurück zum Zitat Jacques T, Picard N, Miller RL, Riemondy KA, Houillier P, Sohet F, et al. Overexpression of pendrin in intercalated cells produces chloride-sensitive hypertension. J Am Soc Nephrol. 2013;24(7):1104–13. This study showed that pendrin overexpression in ICs results in increased sodium chloride absorption in the CD and salt-sensitive elevation of blood pressure. The pressor effect of high salt intake was strictly chloride-dependent, and occurred despite appropriate downregulation of the sodium transporters in the ASDN.PubMedCentralPubMed Jacques T, Picard N, Miller RL, Riemondy KA, Houillier P, Sohet F, et al. Overexpression of pendrin in intercalated cells produces chloride-sensitive hypertension. J Am Soc Nephrol. 2013;24(7):1104–13. This study showed that pendrin overexpression in ICs results in increased sodium chloride absorption in the CD and salt-sensitive elevation of blood pressure. The pressor effect of high salt intake was strictly chloride-dependent, and occurred despite appropriate downregulation of the sodium transporters in the ASDN.PubMedCentralPubMed
78.••
Zurück zum Zitat Gueutin V, Vallet M, Jayat M, Peti-Peterdi J, Corniere N, Leviel F, et al. Renal beta-intercalated cells maintain body fluid and electrolyte balance. J Clin Invest. 2013;123(10):4219–31. This study showed that when the B1-subunit of the H+-ATPase is deleted in mouse, a syndrome of mild distal renal tubular acidosis (RTA) develops which, like the human syndrome, is associated with renal loss of NaCl, K+ and water causing hypovolemia, hypokalemia and polyuria. Sodium wasting was due to a reduction of sodium absorption by the principal cells adjacent to the affected intercalated cells, in addition to the reduction of sodium chloride absorption by the β-intercalated cell itself. The authors discovered that the genetic or pharmacological inactivation of the proton pump caused ATP secretion by β-intercalated cells, which in turn triggers PGE2 release by acting on luminal calcium-coupled purinergic receptors, resulting in inhibition of ENaC in the neighboring PCs.PubMedCentralPubMed Gueutin V, Vallet M, Jayat M, Peti-Peterdi J, Corniere N, Leviel F, et al. Renal beta-intercalated cells maintain body fluid and electrolyte balance. J Clin Invest. 2013;123(10):4219–31. This study showed that when the B1-subunit of the H+-ATPase is deleted in mouse, a syndrome of mild distal renal tubular acidosis (RTA) develops which, like the human syndrome, is associated with renal loss of NaCl, K+ and water causing hypovolemia, hypokalemia and polyuria. Sodium wasting was due to a reduction of sodium absorption by the principal cells adjacent to the affected intercalated cells, in addition to the reduction of sodium chloride absorption by the β-intercalated cell itself. The authors discovered that the genetic or pharmacological inactivation of the proton pump caused ATP secretion by β-intercalated cells, which in turn triggers PGE2 release by acting on luminal calcium-coupled purinergic receptors, resulting in inhibition of ENaC in the neighboring PCs.PubMedCentralPubMed
79.••
Zurück zum Zitat Chambrey R, Kurth I, Peti-Peterdi J, Houillier P, Purkerson JM, Leviel F, et al. Renal intercalated cells are rather energized by a proton than a sodium pump. Proc Natl Acad Sci U S A. 2013;110(19):7928–33. This study shows that the H+‐ ATPase in β-intercalated cells is the major driver of secondary active transport, rather than the Na+,K+ ATPase. This unique feature is the cornerstone for NaCl transport in these cells.PubMedCentralPubMed Chambrey R, Kurth I, Peti-Peterdi J, Houillier P, Purkerson JM, Leviel F, et al. Renal intercalated cells are rather energized by a proton than a sodium pump. Proc Natl Acad Sci U S A. 2013;110(19):7928–33. This study shows that the H+‐ ATPase in β-intercalated cells is the major driver of secondary active transport, rather than the Na+,K+ ATPase. This unique feature is the cornerstone for NaCl transport in these cells.PubMedCentralPubMed
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Zurück zum Zitat Nissant A, Paulais M, Lachheb S, Lourdel S, Teulon J. Similar chloride channels in the connecting tubule and cortical collecting duct of the mouse kidney. Am J Physiol Ren Physiol. 2006;290(6):F1421–9. Nissant A, Paulais M, Lachheb S, Lourdel S, Teulon J. Similar chloride channels in the connecting tubule and cortical collecting duct of the mouse kidney. Am J Physiol Ren Physiol. 2006;290(6):F1421–9.
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Zurück zum Zitat Schultheis PJ, Lorenz JN, Meneton P, Nieman ML, Riddle TM, Flagella M, et al. Phenotype resembling Gitelman’s syndrome in mice lacking the apical Na + −Cl-cotransporter of the distal convoluted tubule. J Biol Chem. 1998;273(44):29150–5.PubMed Schultheis PJ, Lorenz JN, Meneton P, Nieman ML, Riddle TM, Flagella M, et al. Phenotype resembling Gitelman’s syndrome in mice lacking the apical Na + −Cl-cotransporter of the distal convoluted tubule. J Biol Chem. 1998;273(44):29150–5.PubMed
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Zurück zum Zitat Loffing J, Vallon V, Loffing-Cueni D, Aregger F, Richter K, Pietri L, et al. Altered renal distal tubule structure and renal Na(+) and Ca(2+) handling in a mouse model for Gitelman’s syndrome. J Am Soc Nephrol. 2004;15(9):2276–88.PubMed Loffing J, Vallon V, Loffing-Cueni D, Aregger F, Richter K, Pietri L, et al. Altered renal distal tubule structure and renal Na(+) and Ca(2+) handling in a mouse model for Gitelman’s syndrome. J Am Soc Nephrol. 2004;15(9):2276–88.PubMed
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Zurück zum Zitat Nijenhuis T, Hoenderop JG, Loffing J, van der Kemp AW, van Os CH, Bindels RJ. Thiazide-induced hypocalciuria is accompanied by a decreased expression of Ca2+ transport proteins in kidney. Kidney Int. 2003;64(2):555–64.PubMed Nijenhuis T, Hoenderop JG, Loffing J, van der Kemp AW, van Os CH, Bindels RJ. Thiazide-induced hypocalciuria is accompanied by a decreased expression of Ca2+ transport proteins in kidney. Kidney Int. 2003;64(2):555–64.PubMed
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Zurück zum Zitat Vallet M, Picard N, Loffing-Cueni D, Fysekidis M, Bloch-Faure M, Deschenes G, et al. Pendrin regulation in mouse kidney primarily is chloride-dependent. J Am Soc Nephrol. 2006;17(8):2153–63.PubMed Vallet M, Picard N, Loffing-Cueni D, Fysekidis M, Bloch-Faure M, Deschenes G, et al. Pendrin regulation in mouse kidney primarily is chloride-dependent. J Am Soc Nephrol. 2006;17(8):2153–63.PubMed
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Zurück zum Zitat Soleimani M, Barone S, Xu J, Shull GE, Siddiqui F, Zahedi K, et al. Double knockout of pendrin and Na-Cl cotransporter (NCC) causes severe salt wasting, volume depletion, and renal failure. Proc Natl Acad Sci U S A. 2012;109(33):13368–73.PubMedCentralPubMed Soleimani M, Barone S, Xu J, Shull GE, Siddiqui F, Zahedi K, et al. Double knockout of pendrin and Na-Cl cotransporter (NCC) causes severe salt wasting, volume depletion, and renal failure. Proc Natl Acad Sci U S A. 2012;109(33):13368–73.PubMedCentralPubMed
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Zurück zum Zitat Morris RG, Hoorn EJ, Knepper MA. Hypokalemia in a mouse model of Gitelman’s syndrome. Am J Physiol Ren Physiol. 2006;290(6):F1416–20. Morris RG, Hoorn EJ, Knepper MA. Hypokalemia in a mouse model of Gitelman’s syndrome. Am J Physiol Ren Physiol. 2006;290(6):F1416–20.
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Zurück zum Zitat Hadchouel J, Soukaseum C, Busst C, Zhou XO, Baudrie V, Zurrer T, et al. Decreased ENaC expression compensates the increased NCC activity following inactivation of the kidney-specific isoform of WNK1 and prevents hypertension. Proc Natl Acad Sci U S A. 2010;107(42):18109–14.PubMedCentralPubMed Hadchouel J, Soukaseum C, Busst C, Zhou XO, Baudrie V, Zurrer T, et al. Decreased ENaC expression compensates the increased NCC activity following inactivation of the kidney-specific isoform of WNK1 and prevents hypertension. Proc Natl Acad Sci U S A. 2010;107(42):18109–14.PubMedCentralPubMed
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Zurück zum Zitat Lalioti MD, Zhang J, Volkman HM, Kahle KT, Hoffmann KE, Toka HR, et al. Wnk4 controls blood pressure and potassium homeostasis via regulation of mass and activity of the distal convoluted tubule. Nat Genet. 2006;38(10):1124–32.PubMed Lalioti MD, Zhang J, Volkman HM, Kahle KT, Hoffmann KE, Toka HR, et al. Wnk4 controls blood pressure and potassium homeostasis via regulation of mass and activity of the distal convoluted tubule. Nat Genet. 2006;38(10):1124–32.PubMed
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Zurück zum Zitat Castaneda-Bueno M, Cervantes-Perez LG, Vazquez N, Uribe N, Kantesaria S, Morla L, et al. Activation of the renal Na+:Cl- cotransporter by angiotensin II is a WNK4-dependent process. Proc Natl Acad Sci U S A. 2012;109(20):7929–34.PubMedCentralPubMed Castaneda-Bueno M, Cervantes-Perez LG, Vazquez N, Uribe N, Kantesaria S, Morla L, et al. Activation of the renal Na+:Cl- cotransporter by angiotensin II is a WNK4-dependent process. Proc Natl Acad Sci U S A. 2012;109(20):7929–34.PubMedCentralPubMed
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Zurück zum Zitat Deetjen P, Thomas J, Lehrmann H, Kim SJ, Leipziger J. The luminal P2Y receptor in the isolated perfused mouse cortical collecting duct. J Am Soc Nephrol. 2000;11(10):1798–806.PubMed Deetjen P, Thomas J, Lehrmann H, Kim SJ, Leipziger J. The luminal P2Y receptor in the isolated perfused mouse cortical collecting duct. J Am Soc Nephrol. 2000;11(10):1798–806.PubMed
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Zurück zum Zitat Yang T, Schnermann JB, Briggs JP. Regulation of cyclooxygenase-2 expression in renal medulla by tonicity in vivo and in vitro. Am J Physiol. 1999;277(1 Pt 2):F1–9.PubMed Yang T, Schnermann JB, Briggs JP. Regulation of cyclooxygenase-2 expression in renal medulla by tonicity in vivo and in vitro. Am J Physiol. 1999;277(1 Pt 2):F1–9.PubMed
Metadaten
Titel
Relative Roles of Principal and Intercalated Cells in the Regulation of Sodium Balance and Blood Pressure
verfasst von
Régine Chambrey
Francesco Trepiccione
Publikationsdatum
01.04.2015
Verlag
Springer US
Erschienen in
Current Hypertension Reports / Ausgabe 4/2015
Print ISSN: 1522-6417
Elektronische ISSN: 1534-3111
DOI
https://doi.org/10.1007/s11906-015-0538-0

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