loop of henle


Summary: The U-shaped portion of the renal tubule in the KIDNEY MEDULLA, consisting of a descending limb and an ascending limb. It is situated between the PROXIMAL KIDNEY TUBULE and the DISTAL KIDNEY TUBULE.

Top Publications

  1. Esteva Font C, Ars E, Guillen Gomez E, Campistol J, Sanz L, Jimenez W, et al. Ciclosporin-induced hypertension is associated with increased sodium transporter of the loop of Henle (NKCC2). Nephrol Dial Transplant. 2007;22:2810-6 pubmed
    ..The densitometric analysis of the renal immunoblot showed an increase in the Na-K-2Cl cotransporter of the loop of Henle (NKCC2) in cyclosporine-treated rats (178% +/- 36) compared with control rats (100% +/- 18; P < 0.05*)...
  2. Gagnon E, Forbush B, Caron L, Isenring P. Functional comparison of renal Na-K-Cl cotransporters between distant species. Am J Physiol Cell Physiol. 2003;284:C365-70 pubmed
    ..We have also found that the renal NKCC2 of distant vertebrates share similar affinities for cations. This finding points to the existence of highly conserved residues that mediate the kinetic behavior of the NKCC2 splice variants. ..
  3. El Annan J, Brown D, Breton S, Bourgoin S, Ausiello D, Marshansky V. Differential expression and targeting of endogenous Arf1 and Arf6 small GTPases in kidney epithelial cells in situ. Am J Physiol Cell Physiol. 2004;286:C768-78 pubmed
    ..The results provide a framework on which to base and interpret future studies on the role of Arf GTPases in the multitude of cellular trafficking events that occur in renal tubular epithelial cells. ..
  4. Wang T, Sterling H, Shao W, Yan Q, Bailey M, Giebisch G, et al. Inhibition of heme oxygenase decreases sodium and fluid absorption in the loop of Henle. Am J Physiol Renal Physiol. 2003;285:F484-90 pubmed
    ..of chromium mesoporphyrin (CrMP), an inhibitor of HO, on fluid absorption (Jv) and Na+ absorption (JNa) in the loop of Henle and renal clearance methods to examine the effect of CrMP on renal sodium excretion...
  5. Alvarez Guerra M, Garay R. Renal Na-K-Cl cotransporter NKCC2 in Dahl salt-sensitive rats. J Hypertens. 2002;20:721-7 pubmed
    Dahl salt-sensitive (DS) rats are characterized by enhanced NaCl reabsorption in the loop of Henle, but the responsible ion transport protein is unknown...
  6. Gagnon E, Forbush B, Flemmer A, Gimenez I, Caron L, Isenring P. Functional and molecular characterization of the shark renal Na-K-Cl cotransporter: novel aspects. Am J Physiol Renal Physiol. 2002;283:F1046-55 pubmed
  7. Stubbe J, Madsen K, Nielsen F, Skøtt O, Jensen B. Glucocorticoid impairs growth of kidney outer medulla and accelerates loop of Henle differentiation and urinary concentrating capacity in rat kidney development. Am J Physiol Renal Physiol. 2006;291:F812-22 pubmed
    ..We speculate that supranormal exposure to glucocorticoid in the suckling period can alter kidney medullary structure and function permanently. ..
  8. Plata C, Meade P, Hall A, Welch R, Vazquez N, Hebert S, et al. Alternatively spliced isoform of apical Na(+)-K(+)-Cl(-) cotransporter gene encodes a furosemide-sensitive Na(+)-Cl(-)cotransporter. Am J Physiol Renal Physiol. 2001;280:F574-82 pubmed
    ..Thus it is possible that alternative splicing of the BSC1 gene could provide the molecular mechanism enabling the Na(+)-Cl(-)-to-Na(+)-K(+)-2Cl(-) switching in thick ascending limb cells. ..
  9. Paulais M, Lourdel S, Teulon J. Properties of an inwardly rectifying K(+) channel in the basolateral membrane of mouse TAL. Am J Physiol Renal Physiol. 2002;282:F866-76 pubmed
    ..6 and a Hill coefficient of 1.8. Intracellular acidification also reduced the NP(o) of cell-attached patches. This channel is probably a major component of K(+) conductance in the CTAL basolateral membrane. ..

More Information


  1. Stec D, Drummond H, Gousette M, Storm M, Abraham N, Csongradi E. Expression of heme oxygenase-1 in thick ascending loop of henle attenuates angiotensin II-dependent hypertension. J Am Soc Nephrol. 2012;23:834-41 pubmed publisher
    ..To determine the specific contribution of thick ascending loop of Henle (TALH) -derived HO-1, we generated a transgenic mouse in which the uromodulin promoter controlled expression ..
  2. Blau S, Daly L, Fienberg A, Teitelman G, Ehrlich M. DARPP-32 promoter directs transgene expression to renal thick ascending limb of loop of Henle. Am J Physiol. 1995;269:F564-70 pubmed
    ..In the ascending limb of the loop of Henle, DARPP-32 is phosphorylated following stimulation by dopamine and other first messengers, and in this form ..
  3. Yu M, Lopez B, Dos Santos E, Falck J, Roman R. Effects of 20-HETE on Na+ transport and Na+ -K+ -ATPase activity in the thick ascending loop of Henle. Am J Physiol Regul Integr Comp Physiol. 2007;292:R2400-5 pubmed
    ..that 20-hydroxyeicosatetraenoic acid (20-HETE) inhibits Na+ transport in the medullary thick ascending loop of Henle (mTALH), but the mechanisms involved remain uncertain...
  4. Jeck N, Schlingmann K, Reinalter S, Kömhoff M, Peters M, Waldegger S, et al. Salt handling in the distal nephron: lessons learned from inherited human disorders. Am J Physiol Regul Integr Comp Physiol. 2005;288:R782-95 pubmed
    ..As the first line treatment in hyperprostaglandin E syndrome includes cyclooxygenase inhibitors, we propose some hypotheses about the mysterious role of PGE(2) in the etiology of renal salt-losing disorders. ..
  5. Gu R, Wang W. Arachidonic acid inhibits K channels in basolateral membrane of the thick ascending limb. Am J Physiol Renal Physiol. 2002;283:F407-14 pubmed
    ..We conclude that AA inhibits the 50-pS K channel in the basolateral membrane of the mTAL and that the effect of AA is mainly mediated by cytochrome P-450-dependent metabolites of AA. ..
  6. Torp M, Brønd L, Hadrup N, Nielsen J, Praetorius J, Nielsen S, et al. Losartan decreases vasopressin-mediated cAMP accumulation in the thick ascending limb of the loop of Henle in rats with congestive heart failure. Acta Physiol (Oxf). 2007;190:339-50 pubmed
    ..Furthermore, the finding that AT(1) receptor blockade prevents AVP-mediated cAMP accumulation in both SHAM and CHF rats suggests an interaction between angiotensin II and AVP in regulation of mTAL Na reabsorption. ..
  7. Kelsen S, Patel B, Parker L, Vera T, Rimoldi J, Gadepalli R, et al. Heme oxygenase attenuates angiotensin II-mediated superoxide production in cultured mouse thick ascending loop of Henle cells. Am J Physiol Renal Physiol. 2008;295:F1158-65 pubmed publisher
    ..induction of HO-1 can reduce the ANG II-mediated increase in superoxide production in cultured thick ascending loop of Henle (TALH) cells. Studies were performed on an immortalized cell line of mouse TALH (mTALH) cells...
  8. Chadha V, Alon U. Hereditary renal tubular disorders. Semin Nephrol. 2009;29:399-411 pubmed publisher
    ..In this review we address the current knowledge about the association between the genetics and clinical manifestations and treatment of representative disorders affecting the length of the nephron...
  9. Simon D, Bindra R, Mansfield T, Nelson Williams C, Mendonca E, Stone R, et al. Mutations in the chloride channel gene, CLCNKB, cause Bartter's syndrome type III. Nat Genet. 1997;17:171-8 pubmed
    ..These findings demonstrate the critical role of CLCNKB in renal salt reabsorption and blood-pressure homeostasis, and demonstrate the potential role of specific CLCNKB antagonists as diuretic antihypertensive agents. ..
  10. Capasso G, Unwin R, Agulian S, Giebisch G. Bicarbonate transport along the loop of Henle. I. Microperfusion studies of load and inhibitor sensitivity. J Clin Invest. 1991;88:430-7 pubmed
    We microperfused the loop of Henle (LOH) to assess its contribution to urine acidification in vivo...
  11. Jans F, Balut C, Ameloot M, Wouters P, Steels P. Investigation of the Ba2+-sensitive NH4+ transport pathways in the apical cell membrane of primary cultured rabbit MTAL cells. Nephron Physiol. 2007;106:p45-53 pubmed
    ..Indirect immunofluorescence showed the presence of the ROMK protein. In these MTAL cells the Ba(2+)-sensitive component of NH(4)(+) transport is predominant and consists of permeation of NH(4)(+) through an apical ROMK-related channel. ..
  12. Bourgeois S, Massé S, Paillard M, Houillier P. Basolateral membrane Cl(-)-, Na(+)-, and K(+)-coupled base transport mechanisms in rat MTALH. Am J Physiol Renal Physiol. 2002;282:F655-68 pubmed
  13. Shirley D, Walter M, Walter S, Thewles A, Lote C. Renal aluminium handling in the rat: a micropuncture assessment. Clin Sci (Lond). 2004;107:159-65 pubmed
    ..001 in each case), indicating net aluminium reabsorption in the loop of Henle. This reabsorption amounted to 19-26% of the filtered aluminium load...
  14. Moulouel B, Houamel D, Delaby C, Tchernitchko D, Vaulont S, Letteron P, et al. Hepcidin regulates intrarenal iron handling at the distal nephron. Kidney Int. 2013;84:756-66 pubmed publisher
    ..Thus, kidneys exhibit a tissue-specific handling of iron that depends on the extra iron source. Hepcidin may control the expression of iron transporters to prevent renal iron overload. ..
  15. Ramseyer V, Garvin J. Angiotensin II decreases nitric oxide synthase 3 expression via nitric oxide and superoxide in the thick ascending limb. Hypertension. 2009;53:313-8 pubmed publisher
    ..Decreased NOS3 expression by angiotensin II in mTHALs could contribute to increased salt retention observed in angiotensin II-induced hypertension. ..
  16. Cabral P, Herrera M. Membrane-associated aquaporin-1 facilitates osmotically driven water flux across the basolateral membrane of the thick ascending limb. Am J Physiol Renal Physiol. 2012;303:F621-9 pubmed publisher
    The thick ascending limb of the loop of Henle (TAL) reabsorbs ?30% of filtered NaCl but is impermeable to water. The observation that little water traverses the TAL indicates an absence of water channels at the apical membrane...
  17. Plato C, Garvin J. Alpha(2)-adrenergic-mediated tubular NO production inhibits thick ascending limb chloride absorption. Am J Physiol Renal Physiol. 2001;281:F679-86 pubmed
    ..receptors inhibits transport in various nephron segments, and the thick ascending limb of the loop of Henle (THAL) expresses alpha(2)-receptors...
  18. Heyman S, Shina A, Brezis M, Rosen S. Proximal tubular injury attenuates outer medullary hypoxic damage: studies in perfused rat kidneys. Exp Nephrol. 2002;10:259-66 pubmed
    ..51 and -0.72, respectively, p < 0.003). This cogent inverse association might imply that disruption of the proximal nephron attenuates downstream mTAL necrosis by a reduction of distal tubular reabsorptive workload. ..
  19. Singh P, Deng A, Blantz R, Thomson S. Unexpected effect of angiotensin AT1 receptor blockade on tubuloglomerular feedback in early subtotal nephrectomy. Am J Physiol Renal Physiol. 2009;296:F1158-65 pubmed publisher
    ..This cannot be explained by currently known actions of AT(1) receptors but is commensurate with a salutary effect of an intact TGF system on dynamic autoregulation of intraglomerular flow and pressure. ..
  20. Layton A, EDWARDS A. Tubuloglomerular feedback signal transduction in a short loop of henle. Bull Math Biol. 2010;72:34-62 pubmed publisher
  21. Mori T, Ogawa S, Cowely A, Ito S. Role of renal medullary oxidative and/or carbonyl stress in salt-sensitive hypertension and diabetes. Clin Exp Pharmacol Physiol. 2012;39:125-31 pubmed publisher
    ..Oxidative and/or carbonyl stress may be the next target of drug discovery to protect against salt-sensitive hypertension and associated end-organ damage. ..
  22. Takada D, Sekine A, Yabuuchi J, Kogure Y, Ueno T, Yamanouchi M, et al. Renal histology and MRI in a 25-year-old Japanese man with nephronophthisis 4?. Clin Nephrol. 2017;: pubmed publisher
    ..Tubules with cystic dilation were mainly the distal loop of Henle and the distal tubules since immunohistochemical staining was positive for cytokeratin 7 (the distal loop of ..
  23. Michimata M, Fujita S, Araki T, Mizukami K, Kazama I, Muramatsu Y, et al. Reverse pharmacological effect of loop diuretics and altered rBSC1 expression in rats with lithium nephropathy. Kidney Int. 2003;63:165-71 pubmed
    ..Our results suggest that dehydration or high plasma AVP results in an enhanced rBSC1 expression in Li nephropathy, and that rBSC1 expression is closely associated with the adverse effects of Li ions on collecting duct function. ..
  24. Gonzalez Mariscal L, Namorado M, Martin D, Sierra G, Reyes J. The tight junction proteins claudin-7 and -8 display a different subcellular localization at Henle's loops and collecting ducts of rabbit kidney. Nephrol Dial Transplant. 2006;21:2391-8 pubmed
    ..Instead, at the collecting duct, both claudins are present but exhibit a different subcellular distribution. ..
  25. Seyberth H, Schlingmann K. Bartter- and Gitelman-like syndromes: salt-losing tubulopathies with loop or DCT defects. Pediatr Nephrol. 2011;26:1789-802 pubmed publisher
    ..It appears that in most patients with SLT, a combination of solute supplementation with some drug treatment (e.g., indomethacin) is needed for a lifetime. ..
  26. Clarke J, Emson P, Irvine R. Localization of phosphatidylinositol phosphate kinase IIgamma in kidney to a membrane trafficking compartment within specialized cells of the nephron. Am J Physiol Renal Physiol. 2008;295:F1422-30 pubmed publisher
    ..Overall our data suggest that PIP4Kgamma may have a function in the regulation of vesicular transport in specialized kidney epithelial cells. ..
  27. Juncos R, Garvin J. Superoxide enhances Na-K-2Cl cotransporter activity in the thick ascending limb. Am J Physiol Renal Physiol. 2005;288:F982-7 pubmed
    ..Vmax and K1/2 for Na were not affected by O2-. We concluded that O2- stimulates THAL NaCl absorption primarily by enhancing Na entry via Na-K-2Cl cotransport. ..
  28. Westrick K, Serack B, Dantzler W, Pannabecker T. Axial compartmentation of descending and ascending thin limbs of Henle's loops. Am J Physiol Renal Physiol. 2013;304:F308-16 pubmed publisher
    ..We hypothesize that DTLs and ATLs enter and exit CD clusters in an orchestrated fashion that is important for generation of the corticopapillary solute gradient by minimizing NaCl and urea loss. ..
  29. El Achkar T, Wu X, Rauchman M, McCracken R, Kiefer S, Dagher P. Tamm-Horsfall protein protects the kidney from ischemic injury by decreasing inflammation and altering TLR4 expression. Am J Physiol Renal Physiol. 2008;295:F534-44 pubmed publisher
    ..Our data suggest that THP stabilizes the outer medulla in the face of injury by decreasing inflammation, possibly through an effect on TLR4. ..
  30. Pavlov T, Levchenko V, Ilatovskaya D, Moreno C, Staruschenko A. Renal sodium transport in renin-deficient Dahl salt-sensitive rats. J Renin Angiotensin Aldosterone Syst. 2016;17: pubmed publisher
    ..tubules, but did not affect the expression of Na-K-Cl cotransporter (NKCC2), the main transporter in the loop of Henle. In the distal nephron, the expression of sodium chloride cotransporter (NCC) was lower in Ren(-/-) rats...
  31. Lee S, Lee H, Yang H, Thornell I, Bevensee M, Choi I. Sodium-bicarbonate cotransporter NBCn1 in the kidney medullary thick ascending limb cell line is upregulated under acidic conditions and enhances ammonium transport. Exp Physiol. 2010;95:926-37 pubmed publisher
    ..We propose that, in acidic conditions, DIDS-sensitive HCO(3)(-) extrusion is inactivated, while NBCn1 is upregulated to stimulate NH(4)(+) transport. ..
  32. Vallon V, Richter K, Huang D, Rieg T, Schnermann J. Functional consequences at the single-nephron level of the lack of adenosine A1 receptors and tubuloglomerular feedback in mice. Pflugers Arch. 2004;448:214-21 pubmed
    ..is provided for an A1AR-mediated tonic inhibition of Na(+) reabsorption in a water-impermeable segment of the loop of Henle, possibly the thick ascending limb...
  33. Marvao P, de Jesus Ferreira M, Bailly C, Paulais M, Bens M, Guinamard R, et al. Cl- absorption across the thick ascending limb is not altered in cystic fibrosis mice. A role for a pseudo-CFTR Cl- channel. J Clin Invest. 1998;102:1986-93 pubmed
    ..These results show that the 9-pS Cl- channel is distinct from CFTR, and that the CFTR protein has no influence on the Cl- absorption in this part of the renal tubule. ..
  34. Grimm P, Taneja T, Liu J, Coleman R, Chen Y, Delpire E, et al. SPAK isoforms and OSR1 regulate sodium-chloride co-transporters in a nephron-specific manner. J Biol Chem. 2012;287:37673-90 pubmed publisher
    ..As a result of the dependent nature of OSR1 on SPAK in the DCT, NCC is unable to be activated. Consequently, SPAK(-/-) mice are highly sensitive to dietary salt restriction, displaying prolonged negative sodium balance and hypotension. ..
  35. Fenton R, Knepper M. Mouse models and the urinary concentrating mechanism in the new millennium. Physiol Rev. 2007;87:1083-112 pubmed
  36. Chang C, Hung C, Tian Y, Yang C, Wu M. Ciclosporin reduces paracellin-1 expression and magnesium transport in thick ascending limb cells. Nephrol Dial Transplant. 2007;22:1033-40 pubmed
    ..4%. These results suggested that reduced PCLN-1 expression and paracellular Mg2+ transport might play a role in the renal Mg2+ wasting in the CsA tubular effect. ..
  37. El Achkar T, McCracken R, Rauchman M, Heitmeier M, Al Aly Z, Dagher P, et al. Tamm-Horsfall protein-deficient thick ascending limbs promote injury to neighboring S3 segments in an MIP-2-dependent mechanism. Am J Physiol Renal Physiol. 2011;300:F999-1007 pubmed publisher
    ..Our findings raise the interesting possibility of a direct role of basolaterally released THP on regulating inflammation in S3 segments. ..
  38. Meschi M, Detrenis S, Bianchi L, Saccò M, Bertorelli M, Boffetti F, et al. [Loop diuretics: facts and fallacies]. Recenti Prog Med. 2012;103:263-6 pubmed publisher
    ..Several pharmacokinetic and pharmacodynamic strategies are used in this setting, and further research is needed in order to optimize drug effectiveness. ..
  39. Wang T. Renal outer medullary potassium channel knockout models reveal thick ascending limb function and dysfunction. Clin Exp Nephrol. 2012;16:49-54 pubmed publisher
  40. Tomida T, Numaguchi Y, Matsui H, Toki Y, Ito T, Okumura K, et al. Altered expression of prostacyclin synthase in a subset of the thick ascending limb cells and mesangial cells in 5/6-nephrectomized rats. Hypertens Res. 2001;24:411-9 pubmed
    ..In conclusion, our findings suggest that PCS might play an important role in mitigating glomerular hemodynamic changes associated with reduction of renal mass. ..
  41. Cabral P, Hong N, Garvin J. ATP mediates flow-induced NO production in thick ascending limbs. Am J Physiol Renal Physiol. 2012;303:F194-200 pubmed publisher
    ..We conclude that ATP mediates flow-induced NO production in the thick ascending limb likely via activation of P2Y receptors in the luminal and P2X receptors in the basolateral membrane. ..
  42. DI Mari J, Davis R, Safirstein R. MAPK activation determines renal epithelial cell survival during oxidative injury. Am J Physiol. 1999;277:F195-203 pubmed
    ..These results indicate that cell survival in the kidney after ischemia may be dependent on ERK activation, suggesting that this pathway may be a target for therapeutic treatment in I/R injury. ..
  43. Cheng S, Dong J, Pang Y, LaRocca J, Hixon M, Thomas P, et al. Anatomical location and redistribution of G protein-coupled estrogen receptor-1 during the estrus cycle in mouse kidney and specific binding to estrogens but not aldosterone. Mol Cell Endocrinol. 2014;382:950-9 pubmed publisher
    ..markers showed that GPER-1 immunoreactivity primarily resides in distal convoluted tubules and the Loop of Henle (stained with Tamm-Horsfall Protein-1)...
  44. Sonalker P, Jackson E. Norepinephrine, via beta-adrenoceptors, regulates bumetanide-sensitive cotransporter type 1 expression in thick ascending limb cells. Hypertension. 2007;49:1351-7 pubmed
  45. Ramseyer V, Hong N, Garvin J. Tumor necrosis factor ? decreases nitric oxide synthase type 3 expression primarily via Rho/Rho kinase in the thick ascending limb. Hypertension. 2012;59:1145-50 pubmed publisher
    ..These data suggest that some of the beneficial effects of ROCK inhibitors in hypertension could be attributed to the mitigation of TNF-?-induced reduction in NOS3 expression. ..
  46. Haque M, Ares G, Caceres P, Ortiz P. High salt differentially regulates surface NKCC2 expression in thick ascending limbs of Dahl salt-sensitive and salt-resistant rats. Am J Physiol Renal Physiol. 2011;300:F1096-104 pubmed publisher
    NaCl reabsorption by the thick ascending limb of the loop of Henle (THAL) occurs via the apical Na-K-2Cl cotransporter, NKCC2...
  47. Bouley R, Palomino Z, Tang S, Nunes P, Kobori H, LU H, et al. Angiotensin II and hypertonicity modulate proximal tubular aquaporin 1 expression. Am J Physiol Renal Physiol. 2009;297:F1575-86 pubmed publisher
  48. Pham P, Devuyst O, Pham P, Matsumoto N, Shih R, Jo O, et al. Hypertonicity increases CLC-5 expression in mouse medullary thick ascending limb cells. Am J Physiol Renal Physiol. 2004;287:F747-52 pubmed
    ..the kidney, CLC-5 was found to be expressed in the proximal tubule, medullary thick ascending limb (mTAL) of loop of Henle, and intercalated cells of the collecting tubule...
  49. Paredes A, Plata C, Rivera M, Moreno E, Vazquez N, Muñoz Clares R, et al. Activity of the renal Na+-K+-2Cl- cotransporter is reduced by mutagenesis of N-glycosylation sites: role for protein surface charge in Cl- transport. Am J Physiol Renal Physiol. 2006;290:F1094-102 pubmed
    ..Our data demonstrate that NKCC2 is glycosylated and suggest that prevention of glycosylation reduces its functional expression by affecting insertion into the plasma membrane and the intrinsic activity of the cotransporter. ..
  50. Bickel C, Knepper M, Verbalis J, Ecelbarger C. Dysregulation of renal salt and water transport proteins in diabetic Zucker rats. Kidney Int. 2002;61:2099-110 pubmed
    ..This potentially could reduce blood pressure by decreasing proximal tubule sodium reabsorption. ..
  51. Ares G, Caceres P, Ortiz P. Molecular regulation of NKCC2 in the thick ascending limb. Am J Physiol Renal Physiol. 2011;301:F1143-59 pubmed publisher
    ..The thick ascending limb of the loop of Henle (TAL) reabsorbs 25-30% of the NaCl filtered by the glomeruli in a process mediated by the apical Na(+)-K(+)-..
  52. Musso C, Macías Nuñez J. Renal physiology in the oldest old: the Sphinx remakes her question. Int Urol Nephrol. 2005;37:653-4 pubmed
  53. Budu Grajdeanu P, Moore L, Layton H. Effect of tubular inhomogeneities on filter properties of thick ascending limb of Henle's loop. Math Biosci. 2007;209:564-92 pubmed
    We used a simple mathematical model of rat thick ascending limb (TAL) of the loop of Henle to predict the impact of spatially inhomogeneous NaCl permeability, spatially inhomogeneous NaCl active transport, and spatially inhomogeneous ..