Abstract
Background
It has been recently shown that A6 cells exposed to hyponatraemic stress respond with increased sodium uptake via activation of benzamil-sensitive sodium channels. This study was performed, therefore, to explore the possible involvement of benzamil-sensitive sodium channels and cellular sodium influx in brain oedema formation in hyponatraemic rats.
Methods
Four groups of male Wistar rats were studied (n = 13 in each group). Animals in group I with normonatraemia received intracerebroventricular (icv) 0.9% NaCl; animals in group II-IV were made hyponatraemic by intraperitoneal administration of isotonic glucose solution in a dose of 20% per body weight. Rats were pretreated with icv 0.9% NaCl (group II), 120 μg arginine vasopressin (AVP) (group III) or 4 μg benzamil-hydrochloride (group IV). Plasma sodium (ion-selective electrode) plasma osmolality (vapour pressure osmometer) and brain sodium and potassium content (flame photometer) as well as brain water content (desiccation method) were measured after a 2-h hydration period.
Results
Plasma sodium, osmolality and tissue sodium and potassium contents were markedly depressed in hyponatraemic rats (group II-IV, p < 0.0005 for each group) irrespective of drug pretreatment. Brain water content, however, responded to hyponatraemia with an increase from 77.55 ± 1.00% to 78.45 ± 0.94% (p < 0.01), and it was further augmented to 79.35 ± 0.80% (p < 0.0005) by icv AVP pretreatment. By contrast, benzamil administration prevented the rise of brain water caused by hyponatraemia (77.61 ± 1.04%).
Conclusion
Early in the course of hyponatraemia, brain sodium channels may be activated, and the subsequent cellular sodium uptake may generate osmotic gradient to allow passive water flow into the cells. The simultaneous reduction of osmotic water conductivity of brain-specific aquaporin-4 by hyponatraemia, however, may limit water accumulation.
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References
Amiry-Moghaddam M, Ottersen OP (2003) The molecular basis of water transport in the brain. Nat Rev Neurosci 4: 991-1001
Arieff KF(1994) Vasopressin inhibits calcium-coupled sodium efflux system in rat brain. Am J Physiol 266: R1169-R1173
Bindels RJM, Schaffer JA, Reif MC (1988) Stimulation of sodium transport by aldosterone and arginine vasotocin in A6 cells. Biohim Biophys Acta 972:320–330
Canessa CM, Schaffer JA (1992) AVP stimulates Na+ transport in primary cultures of rabbit cortical collecting duct cells. Am J Physiol Renal Fluid Electorlyte Physiol 262:F454–F461
Chen L, Williams SK, Schaffer JA (1990) Differences in synergistic actions of vasopressin and deoxycorticosterone in rat and rabbit CCD. Am J Physiol Renal Fluid Electrolyte Physiol 259:F147–F156
Cserr HF, Latzkovits L (1992) A role for centrally-released vasopressin in brain ion and volume regulation: a hypothesis, in Ermisch A, Landgaf R, Rühle H-J (eds): Progress in Brain Research. Elsevier Sci Publ pp 3-6
DePasquale M, Patlak CS, Cserr HF (1989) Brain ion and volume regulation during acute hyponatremia in Brattleboro rats. Am J Physiol 256: F 1059-F 1066
Djelidi S, Fay M, Cluzenaud F, Escoubet B, Eugene E, Capurro C, Bovalet JP, Farman N (1989) Blot-Chabaud M (1989) Transcriptional regulation of sodium transport by vasopressin in renal cells. J Biol Chem 272:32919–32924
Dóczi T, Szerdahelyi P, Gulya K, Kiss J (1982) Brain water accumulation after the central administration of vasopressin. Neurosurgery 11:402–407
Dóczi T, László FA, Szerdahelyi P, Joo F (1984) Involvement of vasopressin in brain edema formation: further evidence obtained from the Brattleboro diabetes insipidus rat with experimental subarachnoid hemorrhage. Neurosurgery 14:436–441
Ecelbarger CA, Kim G-H, Terris J, Masilamani S, Mitchell C, Reyes I, Verbalis JG, Knepper MA (2000) Vasopressin-mediated regulation of epithelial sodium channel abundance in rat kidney. Am J Physiol Renal Physiol 279:F46–F53
Frind G, Burg MB (1972) Effect of vasopressin on sodium transport in renal cortical collecting duct tubules. Kidney Int 1:224–231
Gunnarson E, Zelenina M, Aperia A (2004) Regulation of brain aquaporins. Neurosci 129:947–955
Han Z, Wax MB, Patil RV (1998) Regulation of aquaporin-4 water channels by phorbol ester-dependent protein phosphorylation. J Biol Chem 273:6001–6004
Hernando F, Choots O, Lolait SJ, Burbach JPH (2001) Immunohistochemical localization of the vasopressin V1B receptor in the rat brain and pituitary gland: Anatomical support for its involvement in the central effect of vasopressin. Endocrinology 142:1659–1668
Kleyman TR, Ernst SA, Coupaye-Gerard B (1994) Arginine vasopressin and forskolin regulate apical cell surface expression of epithelial Na+ channels in A6 cells. Am J Physiol Renal Fluid Electrolyte Physiol 266:F506–F511
Latzkovits L, Cserr HF, Park JT, Cs P, Pettingrew KD, Rimanoczy A (1993) Effects of arginine vasopressin and atriopeptin on glial cell volume measured as 3-MG space. Am J Physiol Cell Physiol 264:C603–C608
Lolait SJ, O’Carroll A-M, Mahan LC, Felder CC, Button DC, Young WC, Mezey É, Brownstein M (1995) Extrapituitary expression of rat V1B vasopressin receptor gene. Proc Natl Acad Sci USA 92:6783–6787
Manley GT, Fujimara M, Ma T, Noshita N, Filiz F, Bollen A, Chan P, Verkman AS (2000) Aquaporin-4 deletion in mice reduces brain oedema following acute water intoxication and ischemic stroke. Nat Med 6:159–163
Nagao S, Kagawa M, Bemana I, Kuniyoshi T, Ogawa T, Honma Y, Kuyama H (1994) Treatment of vasogenic brain edema with arginine vasopressin receptor antagonist an experimental study. Acta Neurochir Suppl (Wien) 60:502–504
Nakhoul NL, Hering-Smith KS, Gambala CT, Hamm LL (1998) Regulation of sodium transport in M-1 cells. Am J Physiol Renal Physiol 275:F998–F1007
Nielsen S, Nagelhus EA, Amiry-Moghaddam M, Bourque C, Agre P ((1997) Specialized membrane domains for water transport in glial cells: high-resolution immunogold cytochemistry of aquaporin-4 in rat brain. J Neurosci 17: 171-180
Niisato N, Post M, VanDriessche W, Marunaka Y (1999) Cell swelling activates stress-activated protein kinases, p38MAPK Kinase and JNK, in renal epithelial A6 cells. Biochem Biophys Res Common 266:547–550
Niisato N, VanDriessche W, Lium MY (2000) Involvement of protein thyrosine kinase in osmoregulation of Na+ transport and membrane capacitance in renal A6 cells. J Member Biol 175:63–77
Niisato N, Eaton DC, Marunaka Y (2004) Involvement of cytosolic Cl- in osmoregulation of α-ENaC gene expression. Am J Physiol Renal Physiol 287:F932–F939
Nishimura M, Ohtsuka K, Nanbu A, Takamashi H (1998) Yoshimura M (2004) Benzamil blockade of brain Na+ channels averts Na+-induced hypertension in rats. Am J Physiol Regulatory Integrative Comp Physiol 274:R635–R644
Nishimura A, Ohtsuka K, Iwai N, Takahashi H, Yoshimura M (1999) Am J Physiol 276:R1416–R1425
Noda M (2007) Hydromineral neuroendocrinology: mechanism of sensing sodium levels in the mammalian brain. Exp Physiol 92:513–522
Pasantes-Morales H, Lezama RA, Ramos-Mandujano G, Tuz KL (2006) Mechanisms of cell volume regulation in hypo-osmolality. Am J Med 119 (7A): S4-S11
Prat AG, Ausiello DA, Cantiello HF (1993) Vasopressin and protein kinase A activate G protein-sensitive epithelial Na+ channels. Am J Physiol Cell Physiol 265:C218–C223
Reif MC, Troutman SL, Schafer JA (1986) Sodium transport by rat cortical collecting tubule. Effects of vasopressin and desoxycorticosterone. J Clin Invest 77:1291–1298
Rosenberg GA, Estrada E, Kyner WT (1990) Vasopressin-induced brain edema is mediated by V1 receptor. Adv Neurol 52:149–154
Saito M, Tamara A, Sugimoto T (1997) 1-Desamino-8-D-arginine vasopressin (DDAVP) as an agonist on V1B vasopressin receptor. Biochem Pharmacol 53:1711–1717
Sarfaraz D, Cl F (1999) Effects of arginine vasopressin on cell volume regulation in brain astrocytes in culture. Am J Physiol Endocrinol Metab 276:E596–E601
Solenov E, Watanabe H, Manley GT, Verkman AS (2004) Sevenfold-reduced osmotic water permeability in primary astrocyte cultures from AQP-4-deficient mice, measured by a fluorescence quenching method. Am J Physiol Cell Physiol 286:C426–C432
Sterns RH, Silves SM (2006) Brain volume regulation in response to hypo-somolality and its correction. Am J Med 119 (7A): S12-S16
Taruno A, Niisato N, Marunaka Y (2007) Hypotonicity stimulates renal epithelial sodium transport by activating JNK via receptor tyrosine kinase. Am J Physiol Renal Physiol 293:F128–F138
Tomita K, Pisano JJ, Knepper MA (1985) Control of sodium and potassim transport in the cortical collecting duct of the rat: Effect of bradykinin, vasopressin, and deoxycorticosterone. J Clin Invest 76:132–136
Vajda Z, Promeneur D, Dóczi T, Sulyok E, Frokiaer J, Ottersen OP, Nielsen S (2000) Increased aquaporin-4 immunoreactivity in rat brain in response to systemic hyponatraemia. Biochem Biophys Res Commun 270:495–503
Vajda Z, Pedersen M, Dóczi T, Sulyok E, Stodkilde-Jorgensen H, Frokiaer J, Nielsen S (2001) Effects of centrally administered arginine vasopressin and atrial natriuretic peptide on the development of brain edema in hyponatraemic rats. Neurosurgery 49:697–704
Vajda Z, Pedersen M, Fuchtbayer EM, Vertz K, Stodkilde-Jorgensen H, Sulyok E, Dóczi T, Neely JD, Agre P, Frokiaer J, Nielsen S (2002) Delayed onset of brain edema and mislocalization of aquaporin-4 in dystrophin-null transgenic mice. Proc Natl Acad Sci USA 99:13131–13136
Wong SM, Chase HS (1988) Effect of vasopressin on intracellular Ca++ and Na+ transport in cultured toad bladder cells. Am J Physiol Fluid Electrolyte Physiol 255:F1015–F1024
Acknowledgement
The study was supported by the Hungarian Ministry of Health (ES) by grant no. ETT 50035 and by the European Human Resources and Mobility (HRM), Marie Curie Research Training Networks (RTN) "Aqua(Glyecero)porin" project.
Authorship Statement
Endre Sulyok and Tamás Dóczi equally contributed to the production of the manuscript by designing the study and writing the paper. József Pál, Zsolt Vajda and Roy Steier performed the animal experiments and laboratory measurements.
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Sulyok, E., Pál, J., Vajda, Z. et al. Benzamil prevents brain water accumulation in hyponatraemic rats. Acta Neurochir 151, 1121–1125 (2009). https://doi.org/10.1007/s00701-009-0354-x
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DOI: https://doi.org/10.1007/s00701-009-0354-x