Seminars in Nephrology
Volume 26, Issue 6 , Pages 404-421 , November 2006

Metabolic Alkalosis, Bedside and Bench

  • Melvin E. Laski

      Affiliations

    • Corresponding Author InformationAddress reprint requests to Melvin E. Laski, MD, TTUHSC, Department of Internal Medicine, Mail Stop 9410, 3601 4th St, Lubbock, TX 79413.
    • ,
  • Sandra Sabatini

References 

  1. Pitts RF, Lottspeich WD. Bicarbonate and the renal regulation of acid-base balance. Am J Physiol. 1946;147:138–154
  2. Pitts RF, Ayer JL, Schiess WA, et al. The renal regulation of acid-base balance in man: III (The reabsorption and excretion of bicarbonate). J Clin Invest. 1949;28:35–44
  3. Cohen JJ. Correction of metabolic alkalosis by the kidney after isometric expansion of extracellular fluid. J Clin Invest. 1968;47:1181–1192
  4. Kassirer JP, Schwartz WB. Correction of metabolic alkalosis in man without repair of potassium deficiency. Am J Med. 1966;40:19–26
  5. Kassirer JP, Berkman PM, Lawrenz DR, et al. The critical role of chloride in the correction of hypokalemic alkalosis in man. Am J Med. 1965;38:172–189
  6. Kurtzman NA. Regulation of renal bicarbonate reabsorption by extracellular volume. J Clin Invest. 1970;49:586–595
  7. Purkerson ML, Lubowitz H, White RW, et al. On the influence of extracellular fluid volume expansion on bicarbonate reabsorption in the rat. J Clin Invest. 1969;48:1754–1760
  8. Kurtzman NA. Relationship of extracellular volume and CO2 tension to renal bicarbonate reabsorption. Am J Physiol. 1970;219:1299–1304
  9. Liu FY, Cogan MG, Rector FC. Axial heterogeneity in the rat proximal convoluted tubule (I. Bicarbonate, chloride, and water transport). Am J Physiol. 1984;247:F816–F821
  10. Rector FC, Carter NW, Seldin DW. The mechanism of bicarbonate reabsorption in the proximal and distal tubules of the kidney. J Clin Invest. 1965;44:278–290
  11. Chan YL, Giebisch G. Relationship between sodium and bicarbonate transport in the rat proximal convoluted tubule. Pflugers Arch. 1980;388:159–164
  12. Rector FC. Sodium, bicarbonate, and chloride absorption by the proximal tubule. Am J Physiol. 1983;244:F461–F471
  13. Clapp JR, Watson JF, Berliner RW. Osmolarity, bicarbonate concentration, and water reabsorption in proximal tubule of the dog nephron. Am J Physiol. 1963;205:273–280
  14. McKinney TD, Burg MB. Bicarbonate and fluid absorption by proximal straight tubules. Kidney Int. 1977;12:1–8
  15. Burg MB, Green N. Bicarbonate transport by isolated perfused rabbit proximal convoluted tubules. Am J Physiol. 1977;233:F307–F314
  16. Alpern RJ, Cogan MG, Rector FC. Effect of luminal bicarbonate concentration on proximal acidification in the rat. Am J Physiol. 1982;243:F53–F59
  17. Preisig PA, Alpern RJ. Contributions of cellular leak pathways to net NaHCO3 and NaCl absorption. J Clin Invest. 1989;83:1859–1867
  18. Alpern RJ, Cogan MG, Rector FC. Effects of extracellular fluid volume and plasma bicarbonate concentration on proximal acidification in the rat. J Clin Invest. 1983;71:736–746
  19. Alpern RJ, Rector FC. A model of proximal tubular bicarbonate absorption. Am J Physiol. 1985;248:F272–F281
  20. Alpern RJ, Cogan MG, Rector FC. Flow dependence of proximal tubular bicarbonate absorption. Am J Physiol. 1983;245:F478–F484
  21. Maddox DA, Gennari FJ. Load dependence of HCO3 and H2O reabsorption in the early proximal tubule of the Munich-Wistar rat. Am J Physiol. 1985;248:F1130;F1121
  22. Bank N, Aynedjian HS, Mutz BF, et al. Evidence for a DCCD-sensitive component of proximal bicarbonate reabsorption. Am J Physiol. 1985;249:F636–F644
  23. Nakhoul NL, Hamm LL. Vacuolar H-ATPase in the kidney. J Nephrol. 2002;15(suppl):S22–S31
  24. Alpern RJ. Cell mechanisms of proximal tubule acidification. Physiol Rev. 1990;70:79–114
  25. Hamm LL. Renal acidification mechanisms. In:  Brenner BM editors. Brenner and Rector’s The Kidney. (ed 7). Philadelphia: Saunders; 2004;p. 497–534
  26. Capasso G, Unwin R, Agulian S, et al. Bicarbonate transport along the loop of Henle (I. Microperfusion studies of load and inhibitor sensitivity). J Clin Invest. 1991;88:430–437
  27. Capasso G, Unwin R, Ciani F, et al. Bicarbonate transport along the loop of Henle (II. Effects of acid-base, dietary and neurohumoral determinants). J Clin Invest. 1994;94:830–838
  28. Good DW. Adaptation of HCO3 and NH4 transport in rat MTAL effects of chronic metabolic acidosis and Na+ intake. Am J Physiol. 1990;258:F1345–F1353
  29. Ullrich KJ, Eigler FW. Sekretion von Wasserstoffionen in den Sammelrohren der Saugertierneiere. Pflugers Arch. 1958;267:491–496
  30. Wang T, Malnic G, Giebisch G, et al. Renal bicarbonate reabsorption in the rat (IV. Bicarbonate transport mechanisms in the early and late distal tubule). J Clin Invest. 1993;91:2776–2784
  31. Wang T, Hropot M, Aronson P, et al. Role of NHE isoforms in medicating bicarbonate reabsorption along the nephron. Am J Physiol. 2001;281:F1117–F1122
  32. Wesson DE. Na/H exchange and H-K ATPase increase distal tubule acidification in chronic alkalosis. Kidney Int. 1998;53:945–951
  33. Iacovitti M, Nash L, Peterson LN, et al. Distal tubule bicarbonate accumulation in vivo (Effect of flow and transtubular bicarbonate gradients). J Clin Invest. 1986;78:1658–1665
  34. Wesson DE. Dietary HCO3 reduces distal tubule acidification by increasing cellular HCO3 secretion. Am J Physiol. 1996;271:F132–F1442
  35. Levine DZ, Vandorpe D, Iacovitti M. Luminal chloride modulates rat distal tubule bidirectional bicarbonate flux in vivo. J Clin Invest. 1990;85:1973;1798
  36. Wesson DE, Dolson GM. Endothelin-1 increases rat distal tubule acidification in vivo. Am J Physiol. 1997;273:F586–F594
  37. Wesson DE, Dolson GM. Augmented bidirectional HCO3 transport by rat distal tubules in chronic alkalosis. Am J Physiol. 1991;261:F308–F317
  38. Wesson DE. Reduced bicarbonate secretion medicates increased distal tubule acidification induced by dietary acid. Am J Physiol. 1996;271:F670–F678
  39. McKinney TD, Burg MB. Bicarbonate transport by rabbit cortical collecting tubules—effect of acid and alkali loads in vivo on transport in vitro. J Clin Invest. 1977;60:766–768
  40. McKinney TD, Burg MB. Bicarbonate secretion by rabbit cortical collecting tubules in vitro. J Clin Invest. 1978;61:1421–1427
  41. McKinney TD, Burg MB. Bicarbonate absorption by rabbit cortical collecting tubules in vitro. Am J Physiol. 1978;234:F141–F145
  42. Laski ME, Warnock DG, Rector FC. Effects of chloride gradients on total CO2 flux in the rabbit cortical collecting tubule. Am J Physiol. 1983;244:F112–F121
  43. Schuster VL. Cyclic adenosine monophosphate-stimulated bicarbonate secretion in rabbit cortical collecting tubules. J Clin Invest. 1985;75:2056–2064
  44. Stone DK, Seldin DW, Kokko JP, et al. Mineralocorticoid modulation of rabbit medullary collecting duct acidification (A sodium-independent effect). J Clin Invest. 1983;72:77–83
  45. Wingo CS. Active proton secretion and potassium absorption in the rabbit outer medullary collecting duct (Functional evidence for proton-potassium-activated adenosine triphosphatase). J Clin Invest. 1989;84:361–365
  46. Eiam-Ong S, Kurtzman NA, Sabatini S. Regulation of collecting tubule adenosine triphosphatases (ATPases) by aldosterone and potassium. J Clin Invest. 1993;91:2385–2392
  47. Relman AS, Schwartz WB. The effect of DOCA on electrolyte balance in normal man and its relation to sodium chloride intake. Yale J Biol Med. 1952;24:540–558
  48. Kassirer JP, London AM, Goldman DM, et al. On the pathogenesis of metabolic alkalosis in hyperaldosteronism. Am J Med. 1970;49:306–315
  49. Lawson NW, Butler GH, Ray CT. Alkalosis and cardiac arrhythmias. Anesth Analg. 1973;52:921–964
  50. Severinghaus JW. Oxyhemoglobin dissociation curve correction for temperature and pH variation in human blood. J Appl Phyiol. 1958;2:485–486
  51. Klocke RA, Bauer C, Forster RE. The kinetics of the oxygen-hemoglobin reactions: Influence of 2,3-diphosphoglycerate (2,3-DPG) and pH. Physiologist. 1970;13:242–246
  52. Arieff AI. Effects of water, acid-base, and electrolyte disorders on the central nervous system. In:  Arieff AI,  DeFronzo RA editor. Fluid Electrolyte and Acid-Base Disorders. New York: Churchill Livingston; 1985;p. 969–1040
  53. Laski ME, Kurtzman NA. Acid-base disorders in medicine. Dis Mo. 1996;XLII:57–128
  54. Luke RG. Metabolic alkalosis: General considerations. In:  Gennari FJ,  Adrogue HJ,  Galla JH, et al. editor. Acid-Base Disorders and Their Treatment. Boca Raton: Taylor and Francis Group; 2005;p. 501–518
  55. Hodgkin JE, Soeprono FF, Chan DM. Incidence of metabolic alkalemia in hospitalized patients. Crit Care Med. 1908;8:725–728
  56. Wilson RF, Gibson D, Percinel AK, et al. Severe alkalosis in critically ill surgical patients. Arch Surg. 1972;105:197–203
  57. Anderson LE, Henrich WL. Alkalemia-associated morbidity and mortality in medical and surgical patients. South Med J. 1987;80:729–733
  58. Galla J. Metabolic alkalosis. In:  DuBose TD,  Hamm LL editor. Acid-Base and Electrolyte Disorders, a Companion to Brenner and Rector’s The Kidney. Philadelphia: Saunders; 2002;p. 109–128
  59. Orwoll ES. The milk-alkali syndrome (Current concepts). Ann Intern Med. 1982;97:242–248
  60. Seldin DW, Rector FC. The generation and maintenance of metabolic alkalosis. Kidney Int. 1972;1:306–321
  61. Kutsogiannis DJ, Noel Gibney RT, Stollery D, et al. Regional citrate versus systemic heparin anticoagulation for continuous renal replacement in critically ill patients. Kidney Int. 2005;67:2361–2367
  62. Towani AJ, Campbell RC, Schenk MB, et al. Simplified citrate anticoagulation for continuous renal replacement. Kidney Int. 2001;60:370–374
  63. Barton CH, Vaziri ND, Ness RL, et al. Cimetidine in the management of metabolic alkalosis induced by nasogastric drainage. Arch Surg. 1979;114:70–74
  64. Bartoli E, Satta A, Faedda R, et al. A furosemide test in the functional evaluation of the human nephron in vivo. J Clin Pharmacol. 1983;23:53–56
  65. Bidet M, Merot J, Tauc M, et al. Na+/H+ exchanger in proximal cells isolated from kidney (II. Short-term regulation by glucocorticoids). Am J Physiol. 1987;253:F945–F951
  66. Damasco MC, Malnic G. Effected of corticosteroids on proximal tubular acidification in the rat. Miner Electrolyte Metab. 1987;13:26–32
  67. Unwin R, Capasso G, Giebisch G. Bicarbonate transport along the loop of Henle: Effect of adrenal steroids. Am J Physiol. 1995;268:F234–F239
  68. Kinsella J, Cudjik T, Sacktor B. Na+-H+ exchange activity in renal brush border membrane vesicles in response to metabolic acidosis; the role of glucocorticoids. Proc Natl Acad Sci U S A. 1984;81:630–634
  69. Hulter H, Licht JH, Bonner EL, et al. Effects of glucocorticoid steroids on renal and systemic acid-base metabolism. Am J Phyisol. 1980;239:F30–F43
  70. Cost WS. A mineralocorticoid syndrome presumably secondary to excessive secretion of corticosterone. Lancet. 1963;1:362–363
  71. Christy NP, Laragh JH. Pathogenesis of hypokalemic metabolic alkalosis in Cushing’s syndrome. N Engl J Med. 1961;265:1083–1088
  72. Schambelan M, Slaton PE, Biglieri EG. Mineralocorticoid production in hyperadrenocorticism (Role in pathogenesis of hypokalemic alkalosis). Am J Med. 1971;51:299–303
  73. Kurtzman NA, Guitierrez LF. Hypothesis: The pathophysiology of Bartter’s syndrome. JAMA. 1975;234:758–759
  74. Greger R. Chloride reabsorption in the rabbit cortical thick ascending limb of the loop of Henle (A Sodium dependent process). Pflugers Arch. 1981;390:38–43
  75. Malnic G, Bailey MA, Giebisch G. Control of renal potassium excretion. In:  Brenner BM editors. Brenner and Rector’s The Kidney. (ed 7). Philadelphia: Saunders; 2004;p. 453–495
  76. Simon DB, Karet FE, Hamden JM, et al. Bartter’s syndrome, hypokalaemic alkalosis with hypercalciuria, is caused by mutation in the Na-K-Cl transporter NKCC2. Nat Genet. 1996;13:183–188
  77. International Collaborative Study Group. Mutations in the gene encoding the inwardly-rectifying renal potassium channel, ROMK, cause the antenatal variant of Bartter’s syndrome: evidence for genetic heterogeneity (International Collaborative Study Group for Bartter-like Syndromes). Hum Mol Genet. 1997;6:17–26
  78. Simon DB, Bindra RS, Mansfield TA, et al. Mutations in the chloride channel gene, CLCNKB, cause Bartter’s syndrome type III. Nat Genet. 1997;17:171–178
  79. Birkenhager R, Otto E, Schurmann MJ, et al. Mutation of BSND causes Bartter syndrome with sensorineural deafness and kidney failure. Nat Genet. 2001;29:310–314
  80. Simon DB, Nelson-Williams C, Bia MJ, et al. Gitelman’s variant of Bartter’s syndrome, inherited hypokalemic alkalosis, is caused by mutations in the thiazide-sensitive Na-Cl cotransporter. Nat Genet. 1996;12:24–30
  81. Lemmink HH, Knoers NVAM, Karolyi L, et al. Novel mutations in the thiazide-sensitive NaCl cotransporter gene in patients with Gitelman syndrome. Kidney Int. 1998;54:720–730
  82. Zelikovic I. Hypokalaemic salt-losing tubulopathies: An evolving story. Nephrol Dial Transplant. 2003;18:1696–1700
  83. Shimkets RA, Warnock DG, Bositis CM, et al. Liddle’s syndrome: Heritable human hypertension caused by mutations in the beta subunit of the epithelial sodium channel. Cell. 1994;79:407–414
  84. Bieberdorf FA, Gordon P, Fordtran JS. Pathogenesis of congenital alkalosis with diarrhea: Implications for the physiology of normal ileal electrolyte absorption and secretion. J Clin Invest. 1972;51:1958–1968
  85. Aichbichler BW, Zerr CH, Santa Ana CA, et al. Proton-pump inhibition of gastric chloride secretion in congenital chloridorrhea. N Engl J Med. 1997;336:106–109
  86. Shnitka TK, Friedman MHW, Kidd EG, et al. Villous tumors of the rectum and colon characterized by severe fluid and electrolyte loss. Surg Gynecol Obstet. 1961;112:609–621
  87. White PC. Disorders of aldosterone biosynthesis and secretion. N Engl J Med. 1994;331:250–258
  88. Chan YL, Biagi B, Giebisch G. Control mechanisms of bicarbonate transport across the rat proximal convoluted tubule. Am J Physiol. 1982;242:F532–F543
  89. Soleimani M, Bergman JA, Hosford MA, et al. Potassium depletion increases luminal Na+/H+ exchange and basolateral Na+:CO=:HCO3- cotransport in the rat renal cortex. J Clin Invest. 1990;86:1076–1083
  90. Adam WR, Koretsky AP, Weiner MW. 31P-NMR in vivo measurement of renal intracellular pH: Effects of acidosis and K+ depletion in rats. Am J Physiol. 1986;251:F904–F910
  91. Suga SI, Phillips MI, Ray PE, et al. Hypokalemia induces renal injury and alterations in vasoactive medicators that favor salt sensitivity. Am J Physiol. 2001;281:F620–F629
  92. Linas SL, Dickman D. Mechanism of the decreased renal blood flow in the potassium-depleted conscious rat. Kidney Int. 1982;21:757–764
  93. Luke RG, Lyerly RH, Anderson J, et al. Effect of potassium depletion on renin release. Kidney Int. 1982;21:14–19
  94. Jones IW, Sebastian A, Hulter H, et al. Systemic and renal acid-base effects of chronic dietary potassium depletion in humans. Kidney Int. 1982;21:402–410
  95. Brunner FP, Frick PG. Hypokalemia, metabolic alkalosis, and hypernatraemia due to “massive” sodium penicillin therapy. BMJ. 1968;4:550–552
  96. Klastersky J, Vaderkelen B, Daneau D, et al. Carbenicillin and hypokalemia. Ann Intern Med. 1973;78:774–775
  97. ED, Medical House Staff. Dynamic aspects of metabolic acid base disturbances: Phenformin lactic acidosis with alkaline overshoot. Trans Assoc Am Physicians. 1972;85:317–324
  98. Okuda Y, Adrogue HJ, Field JB, et al. Counterproductive effects of sodium bicarbonate in diabetic ketoacidosis. J Clin Endrocrinol Metab. 1996;81:314–320
  99. Stinebaugh BJ, Schloeder FX. Glucose-induced alkalosis in fasting subjects. J Clin Invest. 1972;51:1326–1336
  100. Liu F, Cogan M. Angiotensin II (A potent regulator of acidification in the rat early proximal convoluted tubule). J Clin Invest. 1988;82:601–607
  101. Braam M, Mitchell K, Fox J, et al. Proximal tubular secretion of angiotensin II in rats. Am J Physiol. 1993;264:F891–F898
  102. Seikaly M, Arant B, Seney F. Endogenous angiotensin concentrations in specific intrarenal fluid compartments of the rat. J Clin Invest. 1990;86:1352–1357
  103. Rosivall L, Narkates A, Oparil S, et al. De novo intrarenal formation of angiotensin II during control and enhanced renin secretion. Am J Physiol. 1987;252:F1118–F1123
  104. Wolf G, Neilson E. Angiotensin II induces cellular hypertrophy in cultured murine proximal tubular cells. Am J Physiol. 1990;259:F768–F777
  105. Norman J, Badie-Dezfooly B, Nord E, et al. EGF-induced mitogenesis in proximal tubular cells: poetentiation by angiotensin II. Am J Physiol. 1987;253:F299–F309
  106. Edigo J. Vasoactive hormones and renal sclerosis. Kidney Int. 1996;49:587–597
  107. Lopez B, Salom M, Arregui B, et al. Role of superoxide in modulating the renal effects of angiotensin II. Hypertension. 2003;42:1150–1156
  108. Kwon T, Nielsen J, Kim Y, et al. Regulation of sodium transporters in the thick ascending limb of rat kidney: Response to angiotensin II. Am J Physiol. 2003;285:F152–F165
  109. Wall SM, Fischer MP, Glapion DM, et al. AngII reduces net acid secretion in rat outer medullary collecting duct. Am J Physiol. 2003;285:F930–F937
  110. Mount DB, Zandi-Nejad K. Disorders of potassium balance. In:  Brenner BM editors. Brenner and Rector’s The Kidney. (ed 7). Philadelphia: Saunders; 2004;p. 997–1040
  111. Terada Y, Kobayashi T, Kuwana H, et al. Aldosterone stimulates proliferation of mesangial cells by activating mitogen-activated protein incase [1/2], cyclin D1, and cyclin A. J Am Soc Nephrol. 2005;16:2296–2305
  112. Quinkler M, Zehnder D, Eardley K, et al. Increased expression of mineralocorticoid effector mechanisms in kidney biopsies of patients with heavy proteinuria. Circulation. 2006;112:1435–1443
  113. Cha D, Kan Y, Han S, et al. Role of aldosterone in diabetic nephropathy. Nephrol. 2005;10(suppl):S37–S39
  114. Nagai Y, Miyata K, Sun G, et al. Aldosterone stimulates collagen gene expression and synthesis via activation of ERK1/2 in rat renal fibroblasts. Hypertension. 2005;46:1039–1045
  115. Nishikawa T, Suematsu S, Saito J, et al. Human renal mesangial cells produce aldosterone in response to low-density lipoprotein (LDL). J Steroid Biochem Mol Biol. 2005;96:309–316
  116. Good DW, George T, Watts BA. Nongenomic regulation by aldosterone of the epithelial NHE3 Na+/H+ exchanger. Am J Physiol. 2006;290:C757–C763
  117. Wingo C. Active proton secretion and potassium reabsorption in the rabbit outer medullary collecting duct: Functional evidence for proton-potassium-activated adenosine triphosphatase. J Clin Invest. 1989;84:361–365
  118. Rozansky D. The role of aldosterone in renal sodium transport. Sem Nephrol. 2006;26:173–181
  119. Wang J, Barbry P, Maiyar AC, et al. SGK integrates insulin and mineralocorticoid regulation of epithelial sodium transport. Am J Physiol. 2001;280:F303–F313
  120. Park J, Leong ML, Buse P, et al. Serum and glucocorticoid-inducible kinase (SGK) is a target of the PI 3-kinase-stimulated signaling pathway. EMBO J. 1999;18:3024–3033
  121. Kahle K, Wilson F, Lifton R. Regulation of diverse ion transport pathways by WNK4 kinase: A novel molecular switch. Trends Endocrinol Metab. 2005;16:98–103
  122. Gumz M, Popp M, Wingo C, et al. Early transcriptional effects of aldosterone in a mouse inner medullary collecting duct cell line. Am J Physiol. 2003;285:F664–F673
  123. Eiam-Ong S, Laski M, Kurtzman N, et al. Effect of respiratory acidosis and respiratory alkalosis on renal transport enzymes. Am J Physiol. 1994;267:F390–F399
  124. Guntupalli J, Onuigbo M, Wall S, et al. Adaptation to low-K media increases H,K-ATPase but not H-ATPase-mediated pHi recovery in OMCD1 cells. Am J Physiol. 1997;273:C558–C571
  125. Walter R, Heimie-Koib C, Forgo J, et al. Stimulation of Na+/H+ exchange activity by endothelin in opossum kidney cells. Pflugers Arch. 1995;430:137–144
  126. Chu TS, Peng Y, Cano A, et al. EndothelinB receptor activates NHE-3 by a Ca2+-dependent pathway in OKP cells. J Clin Invest. 1996;97:1454–1462
  127. Hosoda J, Hammer RE, Richardson JA, et al. Targeted and natural (piebald-lethal) mutations of endothelin-B receptor gene produce megacolon associated with spotted coat colon in mice. Cell. 1994;79:1267–1276
  128. Laghmani K, Preisig PA, Moe OW, et al. Endothelin-1/endothelin-B receptor-mediated increases in NHE3 activity in chronic metabolic acidosis. J Clin Invest. 2001;107:1563–1569
  129. Ferreira M, Bailly C. Luminal and basolateral endothelin inhibit chloride reabsorption the mouse thick ascending limb via a Ca2+-independent pathway. J Physiol. 1997;505:749–759
  130. Good DW. Sodium-dependent bicarbonate absorption by cortical thick ascending limb of rat kidney. Am J Physiol. 1985;248:F821–F829
  131. Good DW, Di Mari JF, Watts BA. Hypoosmolality stimulates Na+/H+ exchange and HCO3− absorption in thick ascending limb via PI 3-kinase. Am J Physiol. 2000;279:C1443–C1454
  132. Kone B. Nitric oxide synthesis in the kidney: Isoforms, biosynthesis and functions in health. Sem Nephrol. 2004;24:299–315
  133. Wang T, Inglis FM, Kalb RG. Defective fluid and HCO3− absorption in proximal tubule of neuronal nitric oxide synthase-knockout mice. Am J Physiol. 2000;279:F518–F524
  134. Wang T. Role of iNOS and eNOS in modulating proximal tubule transport and acid-base balance. Am J Physiol. 2002;283:F658–F662
  135. Roczniak A, Burns K. Nitric oxide stimulates guanylate cyclase and regulates sodium transport in rabbit proximal tubule. Am J Physiol. 1996;270:F106–F115
  136. Guzman N, Fang M, Tan S, et al. Autocrine inhibition of Na+/K+-ATPase by nitric oxide in mouse proximal tubule epithelial cells. J Clin Invest. 1995;95:2083–2088
  137. Linas S, Repine J. Endothelial cells regulate proximal tubule epithelial cell sodium transport. Kidney Int. 1999;55:1251–1258
  138. Ortiz PA, Hong NJ, Garvin JL. NO decreases thick ascending limb chloride absorption by reducing Na+-K+-2Cl− contratransporter activity. Am J Physiol. 2001;281:F819–F825
  139. Ortiz PA, Garvin JL. Autocrine effects of nitric oxide on HCO3− transport by rat thick ascending limb. Kidney Int. 2000;58:2069–2074
  140. Plato CF, Stoos BA, Wand D, et al. Endogenous nitric oxide inhibits chloride transport in the thick ascending limb. Am J Physiol. 1999;276:F159–F163
  141. Tojo A, Garg LC, Guzman NC, et al. Nitric oxide inhibits bafilomycin-sensitive H+-ATPase activity in rat cortical collecting duct. Am J Physiol. 1994;267:F509–F515
  142. Griffing GT, Komanicky P, Aurecchia SA, et al. Amiloride in Bartter’s syndrome. Clin Pharmacol Ther. 1982;31:713–718
  143. Solomon R, Brown R. Bartter’s syndrome (New insights into pathogenesis and treatment). Am J Med. 1975;59:575–583
  144. Hene RJ, Koomans HA, Boer P, et al. Long-term treatment of Bartter’s syndrome with captopril. BMJ. 1982;285:695
  145. Hene RJ, Koomans HA, Dorhout Mees EJ, et al. Correction of hypokalemia in Bartter’s by enalapril. Am J Kidney Dis. 1987;9:200–205
  146. Verberckmoes R, Van Damme B, Clement J, et al. Bartter’s syndrome with hyperplasia of renomedullary cells: Successful treatment with indomethacin. Kidney Int. 1976;9:302–307
  147. Colussi G, Rombola G, DeFerrari ME, et al. Correction of hypokalemia with antialdosterone therapy in Gitelman’s syndrome. Am J Nephrol. 1994;14:127–135

PII: S0270-9295(06)00111-2

doi: 10.1016/j.semnephrol.2006.09.001

Seminars in Nephrology
Volume 26, Issue 6 , Pages 404-421 , November 2006

Article Tools

* Image Usage & Resolution