Benzamil prevents brain water accumulation in hyponatraemic rats

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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.

Original languageEnglish
Pages (from-to)1121-1125
Number of pages5
JournalActa neurochirurgica
Issue number9
Publication statusPublished - Sep 1 2009


  • Benzamil
  • Brain oedema
  • Hyponatraemia
  • Sodium channel

ASJC Scopus subject areas

  • Surgery
  • Clinical Neurology

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