Increased aquaporin-1 expression in choroid plexus epithelium after systemic hyponatremia.

The expression of aquaporin-1 (AQP1) protein, a water channel, in the choroid plexus epithelium was examined in the rat to determine the role of AQP1 in the pathophysiology of systemic hyponatremia. Systemic hyponatremia was produced by coadministration of 30 ml hypotonic dextrose solution (140 mM) intraperitoneally and 3 microg 1-deamino-8-d-arginine vasopressin (dDAVP) subcutaneously. This hydration protocol produced severe systemic hyponatremia: 2h after drug administration, normonatremic serum osmolarity and Na(+) concentration (296+/-5mOsm/L and 140+/-5 mM) were reduced to 252+/-5mOsm/L and 117+/-2 mM, respectively. AQP1 expression in the third ventricle choroid plexus epithelium was determined by using immunohistochemistry and quantitative immunoblot analysis. After 2h of systemic hyponatremia, AQP1 expression was significantly increased by 28.2+/-2.7% (n=6, P<0.05), whereas it was attenuated to 15.7+/-2.2% (n=6, P<0.05) after 6h of systemic hyponatremia. In addition, TUNEL staining revealed apoptotic granule cells in the dentate gyrus (DG) adjacent to the third ventricle with a peak measured 2h after the start of the systemic hyponatremia protocol, while virtually no apoptotic granule cells left 6h after the start of the hyponatremic treatment. These findings suggest that AQP1-mediated excessive water influx into the brain through the blood-cerebrospinal fluid barrier during systemic hyponatremia may elevate the intracranial pressure and result in the apoptotic brain cell death. Thus, AQP1 in the choroid plexus may play an important role in the pathogenesis of systemic hyponatremia.