Benzamil prevents brain water accumulation in hyponatraemic rats.
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%).


CONCLUSIONS
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.
Institute of Health Promotion and Family Care, Faculty of Health Sciences, University of Pécs, Pécs, Hungary.
Endre
E
Sulyok
József
J
Pál
Zsolt
Z
Vajda
Roy
R
Steier
Tamás
T
Dóczi
D000584:Amiloride / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D000818:Animals; D001127:Arginine Vasopressin / Q000494:pharmacology; D001921:Brain / Q000187:drug effects / Q000378:metabolism / Q000503:physiopathology; D001929:Brain Edema / Q000188:drug therapy* / Q000209:etiology* / Q000503:physiopathology; D004195:Disease Models, Animal; D005947:Glucose / Q000494:pharmacology; D007010:Hyponatremia / Q000150:complications* / Q000378:metabolism / Q000503:physiopathology; D007276:Injections, Intraventricular; D008297:Male; D009994:Osmolar Concentration; D011188:Potassium / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D012964:Sodium / Q000378:metabolism; D015222:Sodium Channels / Q000187:drug effects* / Q000378:metabolism; D012965:Sodium Chloride / Q000494:pharmacology; D014882:Water-Electrolyte Balance / Q000187:drug effects* / Q000502:physiology
D015222:Sodium Channels; C013407:benzamil; D001127:Arginine Vasopressin; D012965:Sodium Chloride; D000584:Amiloride; D012964:Sodium; D005947:Glucose; D011188:Potassium