hypertonic solutions


Summary: Solutions that have a greater osmotic pressure than a reference solution such as blood, plasma, or interstitial fluid.

Top Publications

  1. Burg M, Ferraris J, Dmitrieva N. Cellular response to hyperosmotic stresses. Physiol Rev. 2007;87:1441-74 pubmed
  2. Wehner F, Numata T, Subramanyan M, Takahashi N, Okada Y. Signalling events employed in the hypertonic activation of cation channels in HeLa cells. Cell Physiol Biochem. 2007;20:75-82 pubmed
    ..In contrast, RhoA, PI 3-kinase, ERK 1/2, JNK 1/2 as well as the exocytotic insertion of channels into the plasma membrane are likely not part of the signalling machinery. ..
  3. Sen I, Constable P, Marshall T. Effect of suckling isotonic or hypertonic solutions of sodium bicarbonate or glucose on abomasal emptying rate in calves. Am J Vet Res. 2006;67:1377-84 pubmed
    ..Whether slowing of the abomasal emptying rate in dehydrated diarrheic calves suckling an oral electrolyte solution is clinically important remains to be determined. ..
  4. El Sherbeny A, Naggar H, Miyauchi S, Ola M, Maddox D, Martin P, et al. Osmoregulation of taurine transporter function and expression in retinal pigment epithelial, ganglion, and müller cells. Invest Ophthalmol Vis Sci. 2004;45:694-701 pubmed
    ..The data are relevant to diseases such as diabetes, macular degeneration, and neurodegeneration, in which retinal cell volumes may fluctuate dramatically. ..
  5. Shimizu T, Wehner F, Okada Y. Inhibition of hypertonicity-induced cation channels sensitizes HeLa cells to shrinkage-induced apoptosis. Cell Physiol Biochem. 2006;18:295-302 pubmed
    ..In addition, they provide further evidence for the interplay of proliferation vs. apoptosis and the actual role that mechanisms of cell volume regulation do play in these processes. ..
  6. Liu H, Begley C, Chen M, Bradley A, Bonanno J, McNamara N, et al. A link between tear instability and hyperosmolarity in dry eye. Invest Ophthalmol Vis Sci. 2009;50:3671-9 pubmed publisher
    ..The purpose of this study was to provide indirect evidence of short-term hyperosmolar conditions during tear instability and to test whether the corneal epithelium responds to transient hyperosmolar stress...
  7. Wang L, Dai W, Lu L. Hyperosmotic stress-induced corneal epithelial cell death through activation of Polo-like kinase 3 and c-Jun. Invest Ophthalmol Vis Sci. 2011;52:3200-6 pubmed publisher
  8. Ferenczi E, Fraser J, Chawla S, Skepper J, Schwiening C, Huang C. Membrane potential stabilization in amphibian skeletal muscle fibres in hypertonic solutions. J Physiol. 2004;555:423-38 pubmed
    ..In situations where P(Cl)/P(K) is low, the same co-transporters would instead permit RVIs but at the expense of a capacity to stabilize E(m). ..
  9. Sheikh Hamad D, Gustin M. MAP kinases and the adaptive response to hypertonicity: functional preservation from yeast to mammals. Am J Physiol Renal Physiol. 2004;287:F1102-10 pubmed
    ..This review summarizes the current knowledge about the signaling pathways that regulate the adaptive response to osmotic stress and discusses new insights from yeast that could be relevant to the osmostress response in mammals. ..

More Information


  1. Duranton C, Huber S, Tanneur V, Brand V, Akkaya C, Shumilina E, et al. Organic osmolyte permeabilities of the malaria-induced anion conductances in human erythrocytes. J Gen Physiol. 2004;123:417-26 pubmed
    ..All together, these data should help to resolve ongoing controversy regarding the number of unique channels that exist in P. falciparum-infected erythrocytes. ..
  2. Capó Aponte J, Wang Z, Bildin V, Pokorny K, Reinach P. Fate of hypertonicity-stressed corneal epithelial cells depends on differential MAPK activation and p38MAPK/Na-K-2Cl cotransporter1 interaction. Exp Eye Res. 2007;84:361-72 pubmed
    ..The level of NKCC1 activation affects the extent of cell volume recovery and, in turn, epithelial survival capacity. ..
  3. Fraser J, Wong K, Usher Smith J, Huang C. Membrane potentials in Rana temporaria muscle fibres in strongly hypertonic solutions. J Muscle Res Cell Motil. 2006;27:591-606 pubmed
    ..Indeed, there was no evidence of cation-Cl(-) co-transport activity in strongly hypertonic solutions despite its predicted energetic favourability, suggesting its possible regulation by E (m) in muscle...
  4. Kuper C, Steinert D, Fraek M, Beck F, Neuhofer W. EGF receptor signaling is involved in expression of osmoprotective TonEBP target gene aldose reductase under hypertonic conditions. Am J Physiol Renal Physiol. 2009;296:F1100-8 pubmed publisher
    ..This EGFR-Ras-MAPK pathway contributes to TonEBP transcriptional activation and targets gene expression during osmotic stress, thus establishing a membrane-associated signal input that contributes to the regulation of TonEBP activity. ..
  5. Zhou X, Ferraris J, Burg M. Mitochondrial reactive oxygen species contribute to high NaCl-induced activation of the transcription factor TonEBP/OREBP. Am J Physiol Renal Physiol. 2006;290:F1169-76 pubmed
    ..We conclude that high NaCl increases mitochondrial ROS production, which contributes to the activation of TonEBP/OREBP by increasing its transactivating activity. ..
  6. Bratton S, Chestnut R, Ghajar J, McConnell Hammond F, Harris O, Hartl R, et al. Guidelines for the management of severe traumatic brain injury. II. Hyperosmolar therapy. J Neurotrauma. 2007;24 Suppl 1:S14-20 pubmed
  7. Corrales R, Luo L, Chang E, Pflugfelder S. Effects of osmoprotectants on hyperosmolar stress in cultured human corneal epithelial cells. Cornea. 2008;27:574-9 pubmed publisher
    ..The osmoprotectants L-carnitine and erythritol, alone or in combination, were found to protect against stress activation of corneal epithelial cells cultured in hyperosmolar media. ..
  8. Pham T, Cancio L, Gibran N. American Burn Association practice guidelines burn shock resuscitation. J Burn Care Res. 2008;29:257-66 pubmed publisher
  9. Lang K, Fillon S, Schneider D, Rammensee H, Lang F. Stimulation of TNF alpha expression by hyperosmotic stress. Pflugers Arch. 2002;443:798-803 pubmed
    ..However, the observations in LCL721 cells point to other, TNF alpha-independent, mechanisms mediating apoptotic cell death following an excessive increase of extracellular osmolarity. ..
  10. Rozansky D, Wang J, Doan N, Purdy T, Faulk T, Bhargava A, et al. Hypotonic induction of SGK1 and Na+ transport in A6 cells. Am J Physiol Renal Physiol. 2002;283:F105-13 pubmed
    ..Moreover, these data lend support to the view that SGK1 contributes to the defense of extracellular fluid volume and tonicity in amphibia by mediating a component of the hypotonic induction of distal nephron Na+ transport. ..
  11. Wittwer T, Wahlers T, Fehrenbach A, Elki S, Haverich A. Improvement of pulmonary preservation with Celsior and Perfadex: impact of storage time on early post-ischemic lung function. J Heart Lung Transplant. 1999;18:1198-201 pubmed
  12. Tamas M, Luyten K, Sutherland F, Hernandez A, Albertyn J, Valadi H, et al. Fps1p controls the accumulation and release of the compatible solute glycerol in yeast osmoregulation. Mol Microbiol. 1999;31:1087-104 pubmed
    ..Fps1p may be an example of a more widespread class of regulators of osmoadaptation, which control the cellular content and release of compatible solutes. ..
  13. Shioda R, Reinach P, Hisatsune T, Miyamoto Y. Osmosensitive taurine transporter expression and activity in human corneal epithelial cells. Invest Ophthalmol Vis Sci. 2002;43:2916-22 pubmed
    ..Rises in intracellular taurine do not appear to be essential for osmoregulation, but instead enhance cell survival perhaps through a membrane stabilizer or an antioxidant effect. ..
  14. Launikonis B, Stephenson D. Tubular system volume changes in twitch fibres from toad and rat skeletal muscle assessed by confocal microscopy. J Physiol. 2002;538:607-18 pubmed
  15. Mustafa I, Leverve X. Metabolic and hemodynamic effects of hypertonic solutions: sodium-lactate versus sodium chloride infusion in postoperative patients. Shock. 2002;18:306-10 pubmed
    ..This study demonstrates that hypertonic lactate infusion is safe and well tolerated in patients undergoing elective cardiac surgery. ..
  16. Chawla S, Skepper J, Hockaday A, Huang C. Calcium waves induced by hypertonic solutions in intact frog skeletal muscle fibres. J Physiol. 2001;536:351-9 pubmed
    ..and decreased T-sarcoplasmic reticular (SR) junctional gaps in fibres maintained in and then fixed using hypertonic solutions. 6...
  17. Wehner F, Tinel H. Osmolyte and Na+ transport balances of rat hepatocytes as a function of hypertonic stress. Pflugers Arch. 2000;441:12-24 pubmed
    ..The set-point for the activation of RVI clearly lies below 327 mosmol/l. Na+/H+ antiport is the most sensitive Na+ importer involved in RVI, whereas Na+ conductance plays the prominent role from 360 mosmol/l upwards. ..
  18. Miyakawa H, Woo S, Dahl S, Handler J, Kwon H. Tonicity-responsive enhancer binding protein, a rel-like protein that stimulates transcription in response to hypertonicity. Proc Natl Acad Sci U S A. 1999;96:2538-42 pubmed
  19. Nahm O, Woo S, Handler J, Kwon H. Involvement of multiple kinase pathways in stimulation of gene transcription by hypertonicity. Am J Physiol Cell Physiol. 2002;282:C49-58 pubmed
    ..Tyrosine kinases and phosphatidylinositol 3-kinase also play a significant role. Signaling pathways for stimulation of transcription appeared quite diverse in that each gene was sensitive to different combinations of inhibitors. ..
  20. Neuhofer W, Woo S, Na K, Grunbein R, Park W, Nahm O, et al. Regulation of TonEBP transcriptional activator in MDCK cells following changes in ambient tonicity. Am J Physiol Cell Physiol. 2002;283:C1604-11 pubmed
    ..We conclude that intracellular ionic strength and water content are major factors that determine the activity of TonEBP. ..
  21. Fehrenbach A, Ochs M, Warnecke T, Wahlers T, Wittwer T, Schmiedl A, et al. Beneficial effect of lung preservation is related to ultrastructural integrity of tubular myelin after experimental ischemia and reperfusion. Am J Respir Crit Care Med. 2000;161:2058-65 pubmed
    ..These observations suggest that preservation solutions ameliorate events leading to surfactant disturbance even before extensive lung injury is manifested. ..
  22. Rim J, Atta M, Dahl S, Berry G, Handler J, Kwon H. Transcription of the sodium/myo-inositol cotransporter gene is regulated by multiple tonicity-responsive enhancers spread over 50 kilobase pairs in the 5'-flanking region. J Biol Chem. 1998;273:20615-21 pubmed
    ..We conclude that the sodium/myo-inositol cotransporter gene is regulated by a large region (approximately 50 kilobase pairs) upstream of the gene. ..
  23. Aleu J, Martín Satué M, Navarro P, Pérez de Lara I, Bahima L, Marsal J, et al. Release of ATP induced by hypertonic solutions in Xenopus oocytes. J Physiol. 2003;547:209-19 pubmed
    ..Oocytes injected with an antisense oligonucleotide complementary to CD39 mRNA released less ATP and showed a lower amplitude in the inward current than those oocytes injected with water. ..
  24. Reinehr R, Schliess F, Haussinger D. Hyperosmolarity and CD95L trigger CD95/EGF receptor association and tyrosine phosphorylation of CD95 as prerequisites for CD95 membrane trafficking and DISC formation. FASEB J. 2003;17:731-3 pubmed
    ..This provides a signal for CD95 membrane trafficking and DISC formation. ..
  25. Hung C, LeRoux M, Palmer G, Chao P, Lo S, Valhmu W. Disparate aggrecan gene expression in chondrocytes subjected to hypotonic and hypertonic loading in 2D and 3D culture. Biorheology. 2003;40:61-72 pubmed
  26. Reinehr R, Graf D, Fischer R, Schliess F, Haussinger D. Hyperosmolarity triggers CD95 membrane trafficking and sensitizes rat hepatocytes toward CD95L-induced apoptosis. Hepatology. 2002;36:602-14 pubmed
    ..Hyperosmotic hepatocyte shrinkage induces CD95 trafficking to the plasma membrane, which involves JNK-, PKA-, and PKC-dependent mechanisms and sensitizes hepatocytes toward CD95L-mediated apoptosis. ..
  27. Izumi Y, Nakayama Y, Memetimin H, Inoue T, Kohda Y, Nonoguchi H, et al. Regulation of V2R transcription by hypertonicity and V1aR-V2R signal interaction. Am J Physiol Renal Physiol. 2008;295:F1170-6 pubmed publisher
    ..The counteractivity of V2R and V1aR could be required to maintain minimum urine volume in the dehydrated state. ..
  28. Lang S, Kofke W, Stiefel M. Monitoring and intraoperative management of elevated intracranial pressure and decompressive craniectomy. Anesthesiol Clin. 2012;30:289-310 pubmed publisher
    ..Special consideration is made for the anesthetic management of these patients perioperatively. ..
  29. Zhang Y, Ahmed A, Tran T, Lin J, McFarlane N, Boreham D, et al. The inhibition of endocytosis affects HDL-lipid uptake mediated by the human scavenger receptor class B type I. Mol Membr Biol. 2007;24:442-54 pubmed
    ..These data suggest that that endocytosis is a dynamic regulator of SR-BI's selective lipid uptake activity. ..
  30. Goulenok T, Buzelé R, Duval X, Bruneel F, Stahl J, Fantin B. Management of adult infectious encephalitis in metropolitan France. Med Mal Infect. 2017;47:206-220 pubmed publisher
    ..The aim of this study was to define treatment strategy, empirical and after microbiological documentation at 48hours, through a systematic literature review. ..
  31. Parr A, Walsh P, Truong V, Dutton J. cGMP-Compliant Expansion of Human iPSC Cultures as Adherent Monolayers. Methods Mol Biol. 2016;1357:221-9 pubmed publisher
  32. Numata T, Wehner F, Okada Y. A novel inhibitor of hypertonicity-induced cation channels in HeLa cells. J Physiol Sci. 2007;57:249-52 pubmed
    ..Its efficiency is defined with reference to flufenamic acid (as the most potent blocker so far), both, in whole-cell patch-clamp recordings and in measurements of cell volume regulation. ..
  33. Petrovic S, Barone S, Xu J, Conforti L, Ma L, Kujala M, et al. SLC26A7: a basolateral Cl-/HCO3- exchanger specific to intercalated cells of the outer medullary collecting duct. Am J Physiol Renal Physiol. 2004;286:F161-9 pubmed
    ..02 vs. normal condition). We propose that SLC26A7 is a basolateral Cl-/HCO3- exchanger in intercalated cells of the OMCD and may play an important role in bicarbonate reabsorption in medullary collecting duct. ..
  34. Numata T, Sato K, Okada Y, Wehner F. Hypertonicity-induced cation channels rescue cells from staurosporine-elicited apoptosis. Apoptosis. 2008;13:895-903 pubmed publisher
    ..Our results also demonstrate, for the first time, the ability of the HICC to rescue cells from the process of programmed cell death. ..
  35. Geisberg J, Struhl K. Cellular stress alters the transcriptional properties of promoter-bound Mot1-TBP complexes. Mol Cell. 2004;14:479-89 pubmed
    ..This suggests that functional preinitiation complexes can contain Mot1 instead of TFIIA in vivo. Thus, Mot1-TBP complexes can exist in active and inactive forms that are regulated by environmental stress. ..
  36. Sama R, Ward C, Kaushansky L, Lemay N, Ishigaki S, Urano F, et al. FUS/TLS assembles into stress granules and is a prosurvival factor during hyperosmolar stress. J Cell Physiol. 2013;228:2222-31 pubmed publisher
    ..Intriguingly, cells with reduced expression of FUS exhibit a loss of cell viability in response to sorbitol, indicating a prosurvival role for endogenous FUS in the cellular response to hyperosmolar stress...
  37. Bulger E, May S, Kerby J, Emerson S, Stiell I, Schreiber M, et al. Out-of-hospital hypertonic resuscitation after traumatic hypovolemic shock: a randomized, placebo controlled trial. Ann Surg. 2011;253:431-41 pubmed publisher
    ..However, interpretation of these findings is limited by the early stopping of the trial. Clinical Trials.gov, NCT00316017. ..
  38. Duca W, da Silva R, Arroyo P, Sgnolf A, Cabral C, Ayres D, et al. Liver transplantation using University of Wisconsin or Celsior preserving solutions in the portal vein and Euro-Collins in the aorta. Transplant Proc. 2010;42:429-34 pubmed publisher
    ..19) with hepatic artery thrombosis in 4 (11.1%) CS versus none in the UW group (P = .11). Cadaveric donor OLT showed similar results with organs preserved with UW or Celsior in the portal vein and Euro-Collins in the aorta. ..
  39. Ahmad N, Hostert L, Pratt J, Billar K, Potts D, Lodge J. A pathophysiologic study of the kidney tubule to optimize organ preservation solutions. Kidney Int. 2004;66:77-90 pubmed
    ..Our novel analysis forms the basis of future whole-organ studies that ultimately may allow us to propose an optimum platform for improved preservation solutions. ..
  40. Tanay A, Steinfeld I, Kupiec M, Shamir R. Integrative analysis of genome-wide experiments in the context of a large high-throughput data compendium. Mol Syst Biol. 2005;1:2005.0002 pubmed
    ..Such characterization is impossible when new data sets are studied in isolation. Our results exemplify the power of the integrative approach in the analysis of genomic scale data sets and call for a paradigm shift in their study. ..
  41. Satou R, Nakagawa T, Ido H, Tomomatsu M, Suzuki F, Nakamura Y. Angiotensin III as well as angiotensin II regulates water flow through aquaporins in a clam worm. Biosci Biotechnol Biochem. 2005;69:1221-5 pubmed
    ..Since tetrachloroaurate (III) is a representative blocker of aquaporins, these results indicate that angiotensin III as well as angiotensin II regulates water flow through aquaporins in clam worms. ..
  42. Kim J, Sheen M, Lee S, Jung J, Kwon H. Hypertonicity stimulates PGE2 signaling in the renal medulla by promoting EP3 and EP4 receptor expression. Kidney Int. 2009;75:278-84 pubmed publisher
    ..Kidney International (2009) 75, 278-284. doi:10.1038/ki.2008.498. ..
  43. Yeste M, Briz M, Pinart E, Sancho S, Bussalleu E, Bonet S. The osmotic tolerance of boar spermatozoa and its usefulness as sperm quality parameter. Anim Reprod Sci. 2010;119:265-74 pubmed publisher
  44. Yoshihara M, Guan Z, Littleton J. Differential regulation of synchronous versus asynchronous neurotransmitter release by the C2 domains of synaptotagmin 1. Proc Natl Acad Sci U S A. 2010;107:14869-74 pubmed publisher
    ..These results suggest that the tandem C2 domains of Syt 1 play independent roles in neurotransmission, as Ca(2+) binding to C2A suppresses asynchronous release, whereas Ca(2+) binding to C2B mediates synchronous fusion. ..
  45. LONART G, Simsek Duran F. Deletion of synapsins I and II genes alters the size of vesicular pools and rabphilin phosphorylation. Brain Res. 2006;1107:42-51 pubmed
  46. Brvar M. Chlorobenzylidene malononitrile tear gas exposure: Rinsing with amphoteric, hypertonic, and chelating solution. Hum Exp Toxicol. 2016;35:213-8 pubmed publisher
    ..3 ± 0.5; p = 0.02). CS decontamination with an aqueous, hypertonic, amphoteric, and chelating solution reduces facial pain, whereas prevention with it reduces pain and recovery time. ..
  47. Pihakaski Maunsbach K, Tokonabe S, Vorum H, Rivard C, Capasso J, Berl T, et al. The gamma-subunit of Na-K-ATPase is incorporated into plasma membranes of mouse IMCD3 cells in response to hypertonicity. Am J Physiol Renal Physiol. 2005;288:F650-7 pubmed
    ..We conclude that the gamma-subunit has an important role in the function of Na-K-ATPase to sustain the cellular cation balance over the plasma membrane in a hypertonic environment. ..
  48. Monlezun S, Ouali S, Poulain D, Theodosis D. Polysialic acid is required for active phases of morphological plasticity of neurosecretory axons and their glia. Mol Cell Neurosci. 2005;29:516-24 pubmed
    ..PSA, therefore, by promoting dynamic cell interactions, is necessary for plasticity of axons and their associated glia. ..
  49. Holt M, King S, Cala P, Pedersen S. Regulation of the Pleuronectes americanus Na+/H+ exchanger by osmotic shrinkage, beta-adrenergic stimuli, and inhibition of Ser/Thr protein phosphatases. Cell Biochem Biophys. 2006;45:1-18 pubmed
    ..It is suggested that paNHE1 activation by osmotic shrinkage and by PP1/PP2A inhibition involves partially convergent signaling pathways, whereas activation of paNHE1 by beta-adrenergic stimuli is mediated by a separate pathway. ..
  50. Blanco J, Long J, Gee G, Donoghue A, Wildt D. Osmotic tolerance of avian spermatozoa: influence of time, temperature, cryoprotectant and membrane ion pump function on sperm viability. Cryobiology. 2008;56:8-14 pubmed
    ..Differences are independent of the role of osmotic pumps in these species. ..
  51. Ogura T, Matsuda H, Shibamoto T, Imanishi S. Osmosensitive properties of rapid and slow delayed rectifier K+ currents in guinea-pig heart cells. Clin Exp Pharmacol Physiol. 2003;30:616-22 pubmed
    ..These results, together with the reported IK stimulation by hyposmotic cell swelling, provide further support for cell volume-sensitive properties of cardiac electrical activity. ..
  52. Habicher M, Perrino A, Spies C, von Heymann C, Wittkowski U, Sander M. Contemporary fluid management in cardiac anesthesia. J Cardiothorac Vasc Anesth. 2011;25:1141-53 pubmed publisher
  53. Beppu N, Higure Y, Mashiyama K, Ohtubo Y, Kumazawa T, Yoshii K. Hypertonicity augments bullfrog taste nerve responses to inorganic salts. Pflugers Arch. 2012;463:845-51 pubmed publisher
    ..We quantitatively suggest that both the enhancing and suppressing effects result from the magnitude and direction of local circuit currents generated by diffusion potentials across tight junctions surrounding taste receptor cells. ..