期刊论文详细信息
BMC Nephrology
Effect of volume expansion with hypertonic- and isotonic saline and isotonic glucose on sodium and water transport in the principal cells in the kidney
Erling B Pedersen2  Soren Nielsen1  Jesper N Bech2  Frank H Mose2  Janni M Jensen2 
[1]Water and Salt Research Centre, Aarhus University, Aarhus, Denmark
[2]Aarhus University, Aarhus, Denmark
关键词: Renin-angiotensin-aldosterone system;    Arginine vasopressin;    Epithelial sodium channels;    Aquaporin2;    Urination;    Healthy subjects;   
Others  :  1082837
DOI  :  10.1186/1471-2369-14-202
 received in 2013-06-20, accepted in 2013-09-23,  发布年份 2013
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【 摘 要 】

Background

The renal distal nephron plays an important role in the maintenance of sodium balance, extra cellular volume and blood pressure. The degree of water transport, via aquaporin2 water channels (AQP2), and sodium transport, via epithelial sodium channels (ENaC) in renal collecting duct principal cells are reflected by the level of urinary excretion of AQP2 (u-AQP2) and the γ-fraction of ENaC (u-ENaCγ). The effects of an acute intravenous volume load with isotonic saline, hypertonic saline and glucose on u-AQP2, u-ENaCγ and underlying mechanisms have never been studied in a randomized, placebo-controlled trial in healthy humans.

Methods

We studied the effects of 0.9% saline (23 ml/kg), 3% saline (7 ml/kg) and 5% glucose (23 ml/kg) on u-AQP2 and u-ENaCγ, fractional sodium excretion (FENa), free water clearance (CH2O), and plasma concentrations of vasopressin (AVP), renin (PRC), angiotensin II (ANG II) and aldosterone (Aldo) in a randomized, crossover study of 23 healthy subjects, who consumed a standardized diet, regarding calories, sodium and fluid for 4 days before each examination day.

Results

After isotonic saline infusion, u-AQP2 increased (27%). CH2O and u-ENaCγ were unchanged, whereas FENa increased (123%). After hypertonic saline infusion, there was an increase in u-AQP2 (25%), u-ENaCγ (19%) and FENa (96%), whereas CH2O decreased (-153%). After isotonic glucose infusion, there was a decrease in u-AQP2 (-16%), ENaCγ (-10%) and FENa (-44%) whereas CH2O increased (164%). AVP remained unchanged after isotonic saline and glucose, but increased after hypertonic saline (139%). PRC, AngII and p-Aldo decreased after isotonic and hypertonic saline infusion, but not after glucose infusion.

Conclusions

Volume expansion with 3% and 0.9% saline increased u-AQP2, while isotonic glucose decreased u-AQP2. Infusion of hypertonic saline increased u-ENaCγ, whereas u-ENaCγ was not significantly changed after isotonic saline and tended to decrease after glucose. Thus, the transport of water and sodium is changed both via the aquaporin 2 water channels and the epithelial sodium channels during all three types of volume expansion to regulate and maintain water- and sodium homeostasis in the body.

Trial registration

Clinical Trial no: NCT01414088

【 授权许可】

   
2013 Jensen et al.; licensee BioMed Central Ltd.

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Figure 2.

【 参考文献 】
  • [1]Rossier BC, Canessa CM, Schild L, Horisberger JD: Epithelial sodium channels. Curr Opin Nephrol Hypertens 1994, 3(5):487-496.
  • [2]Buemi M, Nostro L, Di Pasquale G, Cavallaro E, Sturiale A, Floccari F, Aloisi C, Ruello A, Calapai G, Corica F, Frisina N: Aquaporin-2 water channels in spontaneously hypertensive rats. Am J Hypertens 2004, 17(12 Pt 1):1170-1178.
  • [3]Su YR, Menon AG: Epithelial sodium channels and hypertension. Drug Metab Dispos 2001, 29(4 Pt 2):553-556.
  • [4]Nielsen S, Kwon TH, Frokiaer J, Knepper MA: Key roles of renal aquaporins in water balance and water-balance disorders. News Physiol Sci 2000, 15:136-143.
  • [5]Rossier BC, Pradervand S, Schild L, Hummler E: Epithelial sodium channel and the control of sodium balance: interaction between genetic and environmental factors. Annu Rev Physiol 2002, 64:877-897.
  • [6]Pedersen RS, Bentzen H, Bech JN, Pedersen EB: Effect of water deprivation and hypertonic saline infusion on urinary AQP2 excretion in healthy humans. Am J Physiol Renal Physiol 2001, 280(5):F860-7.
  • [7]Graffe CC, Bech JN, Pedersen EB: Effect of high and low sodium intake on urinary aquaporin-2 excretion in healthy humans. Am J Physiol Renal Physiol 2012, 302(2):F264-75.
  • [8]Lauridsen TG, Vase H, Starklint J, Bech JN, Pedersen EB: Protein-enriched diet increases water absorption via the aquaporin-2 water channels in healthy humans. Nephrol Dial Transplant 2010, 25(8):2502-2510.
  • [9]Matthesen SK, Larsen T, Vase H, Lauridsen TG, Jensen JM, Pedersen EB: Effect of amiloride and spironolactone on renal tubular function and central blood pressure in patients with arterial hypertension during baseline conditions and after furosemide: a double-blinded, randomized, placebo-controlled crossover trial. Clin Exp Hypertens 2012, 35(5):313.
  • [10]Hager H, Kwon TH, Vinnikova AK, Masilamani S, Brooks HL, Frokiaer J, Knepper MA, Nielsen S: Immunocytochemical and immunoelectron microscopic localization of alpha-, beta-, and gamma-ENaC in rat kidney. Am J Physiol Renal Physiol 2001, 280(6):F1093-106.
  • [11]Kwon TH, Hager H, Nejsum LN, Andersen ML, Frokiaer J, Nielsen S: Physiology and pathophysiology of renal aquaporins. Semin Nephrol 2001, 21(3):231-238.
  • [12]Nielsen S: Renal aquaporins: an overview. BJU Int 2002, 90(Suppl 3):1-6.
  • [13]DiGiovanni SR, Nielsen S, Christensen EI, Knepper MA: Regulation of collecting duct water channel expression by vasopressin in Brattleboro rat. Proc Natl Acad Sci U S A 1994, 91(19):8984-8988.
  • [14]Nielsen S, Chou CL, Marples D, Christensen EI, Kishore BK, Knepper MA: Vasopressin increases water permeability of kidney collecting duct by inducing translocation of aquaporin-CD water channels to plasma membrane. Proc Natl Acad Sci U S A 1995, 92(4):1013-1017.
  • [15]Wen H, Frokiaer J, Kwon TH, Nielsen S: Urinary excretion of aquaporin-2 in rat is mediated by a vasopressin-dependent apical pathway. J Am Soc Nephrol 1999, 10(7):1416-1429.
  • [16]Kanno K, Sasaki S, Hirata Y, Ishikawa S, Fushimi K, Nakanishi S, Bichet DG, Marumo F: Urinary excretion of aquaporin-2 in patients with diabetes insipidus. N Engl J Med 1995, 332(23):1540-1545.
  • [17]Saito T, Ishikawa SE, Sasaki S, Nakamura T, Rokkaku K, Kawakami A, Honda K, Marumo F, Saito T: Urinary excretion of aquaporin-2 in the diagnosis of central diabetes insipidus. J Clin Endocrinol Metab 1997, 82(6):1823-1827.
  • [18]Elliot S, Goldsmith P, Knepper M, Haughey M, Olson B: Urinary excretion of aquaporin-2 in humans: a potential marker of collecting duct responsiveness to vasopressin. J Am Soc Nephrol 1996, 7(3):403-409.
  • [19]Pisitkun T, Shen RF, Knepper MA: Identification and proteomic profiling of exosomes in human urine. Proc Natl Acad Sci U S A 2004, 101(36):13368-13373.
  • [20]Rai T, Sekine K, Kanno K, Hata K, Miura M, Mizushima A, Marumo F, Sasaki S: Urinary excretion of aquaporin-2 water channel protein in human and rat. J Am Soc Nephrol 1997, 8(9):1357-1362.
  • [21]Pedersen RS, Bentzen H, Bech JN, Nyvad O, Pedersen EB: Urinary aquaporin-2 in healthy humans and patients with liver cirrhosis and chronic heart failure during baseline conditions and after acute water load. Kidney Int 2003, 63(4):1417-1425.
  • [22]Baumgarten R, van de Pol MH, Deen PM, van Os CH, Wetzels JF: Dissociation between urine osmolality and urinary excretion of aquaporin-2 in healthy volunteers. Nephrol Dial Transplant 2000, 15(8):1155-1161.
  • [23]Hasler U, Nunes P, Bouley R, Lu HA, Matsuzaki T, Brown D: Acute hypertonicity alters aquaporin-2 trafficking and induces a MAPK-dependent accumulation at the plasma membrane of renal epithelial cells. J Biol Chem 2008, 283(39):26643-26661.
  • [24]Marples D, Christensen BM, Frokiaer J, Knepper MA, Nielsen S: Dehydration reverses vasopressin antagonist-induced diuresis and aquaporin-2 downregulation in rats. Am J Physiol 1998, 275(3 Pt 2):F400-9.
  • [25]DIRKS JH, CIRKSENA WJ, BERLINER RW: The effects of saline infusion on sodium reabsorption by the proximal tubule of the Dog. J Clin Invest 1965, 44:1160-1170.
  • [26]de Bold AJ, Borenstein HB, Veress AT, Sonnenberg H: A rapid and potent natriuretic response to intravenous injection of atrial myocardial extract in rats. Life Sci 1981, 28(1):89-94.
  • [27]Singer DR, Shore AC, Markandu ND, Buckley MG, Sagnella GA, MacGregor GA: Dissociation between plasma atrial natriuretic peptide levels and urinary sodium excretion after intravenous saline infusion in normal man. Clin Sci (Lond) 1987, 73(3):285-289.
  • [28]Pedersen EB, Thomsen IM, Lauridsen TG: Abnormal function of the vasopressin-cyclic-AMP-aquaporin2 axis during urine concentrating and diluting in patients with reduced renal function. A case control study. BMC Nephrol 2010, 11:26. BioMed Central Full Text
  • [29]Saito T, Higashiyama M, Nakamura T, Kusaka I, Nagasaka S, Saito T, Ishikawa S: Urinary excretion of the aquaporin-2 water channel exaggerated in pathological states of impaired water excretion. Clin Endocrinol (Oxf) 2001, 55(2):217-221.
  • [30]Reaux A, De Mota N, Skultetyova I, Lenkei Z, El Messari S, Gallatz K, Corvol P, Palkovits M, Llorens-Cortes C: Physiological role of a novel neuropeptide, apelin, and its receptor in the rat brain. J Neurochem 2001, 77(4):1085-1096.
  • [31]De Mota N, Reaux-Le Goazigo A, El Messari S, Chartrel N, Roesch D, Dujardin C, Kordon C, Vaudry H, Moos F, Llorens-Cortes C: Apelin, a potent diuretic neuropeptide counteracting vasopressin actions through inhibition of vasopressin neuron activity and vasopressin release. Proc Natl Acad Sci U S A 2004, 101(28):10464-10469.
  • [32]Azizi M, Iturrioz X, Blanchard A, Peyrard S, De Mota N, Chartrel N, Vaudry H, Corvol P, Llorens-Cortes C: Reciprocal regulation of plasma apelin and vasopressin by osmotic stimuli. J Am Soc Nephrol 2008, 19(5):1015-1024.
  • [33]Edinger RS, Bertrand CA, Rondandino C, Apodaca GA, Johnson JP, Butterworth MB: The epithelial sodium channel (ENaC) establishes a trafficking vesicle pool responsible for its regulation. PLoS One 2012, 7(9):e46593.
  • [34]Ecelbarger CA, Kim GH, Terris J, Masilamani S, Mitchell C, Reyes I, Verbalis JG, Knepper MA: Vasopressin-mediated regulation of epithelial sodium channel abundance in rat kidney. Am J Physiol Renal Physiol 2000, 279(1):F46-53.
  • [35]Schild L: The epithelial sodium channel and the control of sodium balance. Biochim Biophys Acta 2010, 1802(12):1159-1165.
  • [36]Butterworth MB: Regulation of the epithelial sodium channel (ENaC) by membrane trafficking. Biochim Biophys Acta 2010, 1802(12):1166-1177.
  • [37]Garty H, Palmer L: Epithelial sodium channels: function, structure and regulation. Physiol Rev 1997, 77(2):359-396.
  • [38]Andersen LJ, Andersen JL, Schutten HJ, Warberg J, Bie P: Antidiuretic effect of subnormal levels of arginine vasopressin in normal humans. Am J Physiol 1990, 259(1 Pt 2):R53-60.
  • [39]Bankir L, Fernandes S, Bardoux P, Bouby N, Bichet DG: Vasopressin-V2 receptor stimulation reduces sodium excretion in healthy humans. J Am Soc Nephrol 2005, 16(7):1920-1928.
  • [40]Ecelbarger CA, Kim GH, Wade JB, Knepper MA: Regulation of the abundance of renal sodium transporters and channels by vasopressin. Exp Neurol 2001, 171(2):227-234.
  • [41]Bugaj V, Pochynyuk O, Stockand JD: Activation of the epithelial Na + channel in the collecting duct by vasopressin contributes to water reabsorption. Am J Physiol Renal Physiol 2009, 297(5):F1411-8.
  • [42]Perucca J, Bichet DG, Bardoux P, Bouby N, Bankir L: Sodium excretion in response to vasopressin and selective vasopressin receptor antagonists. J Am Soc Nephrol 2008, 19(9):1721-1731.
  • [43]Stockand JD: Vasopressin regulation of renal sodium excretion. Kidney Int 2010, 78(9):849-856.
  • [44]Lauridsen TG, Vase H, Bech JN, Nielsen S, Pedersen EB: Direct effect of methylprednisolone on renal sodium and water transport via the principal cells in the kidney. Eur J Endocrinol 2010, 162(5):961-969.
  • [45]Lauridsen TG, Vase H, Starklint J, Graffe CC, Bech JN, Nielsen S, Pedersen EB: Increased renal sodium absorption by inhibition of prostaglandin synthesis during fasting in healthy man. A possible role of the epithelial sodium channels. BMC Nephrol 2010, 11:28. BioMed Central Full Text
  • [46]Matthesen SK, Larsen T, Vase H, Lauridsen TG, Pedersen EB: Effect of potassium supplementation on renal tubular function, ambulatory blood pressure and pulse wave velocity in healthy humans. Scand J Clin Lab Invest 2012, 72(1):78-86.
  • [47]Kim GH, Masilamani S, Turner R, Mitchell C, Wade JB, Knepper MA: The thiazide-sensitive Na-Cl cotransporter is an aldosterone-induced protein. Proc Natl Acad Sci U S A 1998, 95(24):14552-14557.
  • [48]Sandberg MB, Riquier AD, Pihakaski-Maunsbach K, McDonough AA, Maunsbach AB: ANG II provokes acute trafficking of distal tubule Na + -Cl(-) cotransporter to apical membrane. Am J Physiol Renal Physiol 2007, 293(3):F662-9.
  • [49]Pedersen NB, Hofmeister MV, Rosenbaek LL, Nielsen J, Fenton RA: Vasopressin induces phosphorylation of the thiazide-sensitive sodium chloride cotransporter in the distal convoluted tubule. Kidney Int 2010, 78(2):160-169.
  • [50]Svensen CH, Waldrop KS, Edsberg L, Hahn RG: Natriuresis and the extracellular volume expansion by hypertonic saline. J Surg Res 2003, 113(1):6-12.
  • [51]Andersen LJ, Andersen JL, Pump B, Bie P: Natriuresis induced by mild hypernatremia in humans. Am J Physiol Regul Integr Comp Physiol 2002, 282(6):R1754-61.
  • [52]Castaneda-Bueno M, Arroyo JP, Gamba G: Independent regulation of Na + and K + balance by the kidney. Med Princ Pract 2012, 21(2):101-114.
  • [53]Giebisch GH: A trail of research on potassium. Kidney Int 2002, 62(5):1498-1512.
  • [54]Butterworth MB, Edinger RS, Frizzell RA, Johnson JP: Regulation of the epithelial sodium channel by membrane trafficking. Am J Physiol Renal Physiol 2009, 296(1):F10-24.
  • [55]Butterworth MB, Edinger RS, Johnson JP, Frizzell RA: Acute ENaC stimulation by cAMP in a kidney cell line is mediated by exocytic insertion from a recycling channel pool. J Gen Physiol 2005, 125(1):81-101.
  • [56]Damkjaer M, Isaksson GL, Stubbe J, Jensen BL, Assersen K, Bie P: Renal renin secretion as regulator of body fluid homeostasis. Pflugers Arch 2012, 465(1):153.
  • [57]Loffing J, Korbmacher C: Regulated sodium transport in the renal connecting tubule (CNT) via the epithelial sodium channel (ENaC). Pflugers Arch 2009, 458(1):111-135.
  • [58]Andersen LJ, Jensen TU, Bestle MH, Bie P: Isotonic and hypertonic sodium loading in supine humans. Acta Physiol Scand 1999, 166(1):23-30.
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