Altered Expression of eNOS and VEGF in the Rat Choroid Plexus following Systemic Hyponatremia / 대한해부학회지

ABSTRACT

In the present study, alterations of the endothelial nitric oxide synthase (eNOS) and the vascular endothelial growth factor (VEGF) expression in the third ventricle choroid plexus and their effects to the adjacent hippocampus were studied in the systemic hyponatremic model with the total of 29 adult male Spraque-Dawley rats. Systemic hyponatremia was induced by the coadministration of 30mL(~12% body weight) dextrose solution (140 mmol/L) intraperitoneally and a 3-microgram subcutaneous dose of 1-deamino-8-D-arginine vasopressin (dDAVP). Two and six hours after the drug administration, there were significant reductions in the serum osmolarity (252+/-5.1 and 252+/-6.4 mOsm /L) and in Na+ concentration (117+/-1.7 and 97.2 mM) from the control values (osmolarity 296+/-5.2 mOsm/L, Na+ concentration 140+/-4.7 mM). The expression levels of eNOS and VEGF protein in the choroid plexus were determined by using immunohistochemistry and quantitative immunoblotting. There was a significant increase in the expression of the eNOS (135%+/-2%, P<0.05), whereas the expression of the VEGF was slightly increased compared with the control rats after 2 h of systemic hyponatremia. 6 h after the onset of systemic hyponatremia, expression of the eNOS and the VEGF was decreased simultaneously. Consistent with the expression of the eNOS in choroid plexus after 2 h after systemic hyponatremia, cresyl violet staining revealed necrotic cell death in the hippocampus CA3 subfield, presumably resulting from cerebrospinal fluid (CSF) overproduction and subsequent an elevation of intracranial pressure. Thus, activation of the eNOS protein in the choroid plexus may be one of the molecular mechanisms of the hippocampal cell injury. Additionally, substantial decrease of eNOS and VEGF expression in the choroid plexus after 6 h of the systemic hyponatremia may reflect the eNOS and VEGF in response to the systemic hyponatremia undergo the regulatory changes to prevent the overproduction of CSF. Overall, these results suggest that NO-mediated excessive water influx into the ventricle is important for the cerebral pathogenesis after the systemic hyponatremia.