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Benzamil Prevents Brain Water Accumulation in Hyponatraemic Rats

Benzamil Prevents Brain Water Accumulation in Hyponatraemic Rats

Endre Sulyok, József Pál, Zsolt Vajda, Roy Steier, Tamás Dóczi

Acta Neurochir (Wien). 2009 Sep;151(9):1121-5.

PMID: 19415169

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 microg arginine vasopressin (AVP) (group III) or 4 microg 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.

Chemicals Related in the Paper:

Catalog Number	Product Name	Structure	CAS Number	Price
ALP161804202	Benzamil hydrochloride hydrate		161804-20-2 (anhydrous)	Price

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