Sodium Transport in the Choroid Plexus and Salt-Sensitive Hypertension

Abstract

Abstract-To elucidate the role of epithelial sodium channels (ENaCs) and Na ϩ -K ϩ -ATPase in Na ϩ transport by the choroid plexus, we studied ENaC expression and Na ϩ transport in the choroid plexus. Lateral ventricle choroid plexuses were obtained from young male Wistar, Dahl salt-resistant (SS.BN13), and Dahl salt-sensitive (SS/MCW) rats on a regular (0.3%) or high-(8.0%) salt diet. The effects of ENaC blocker benzamil and Na ϩ -K ϩ -ATPase blocker ouabain on sodium transport were evaluated by measuring the amounts of retained 22 Na ϩ and by evaluating intracellular [Na ϩ ] with Sodium Green fluorescence. In Wistar rats, ENaC distribution was as follows: microvilli, 10% to 30%; cytoplasm, 60% to 80%; and basolateral membrane, 5% to 10%. Benzamil (10 Ϫ8 Key Words: sodium Ⅲ choroid plexus Ⅲ ENaC Ⅲ Na ϩ -K ϩ -ATPase Ⅲ Dahl rats Ⅲ hypertension S trict regulation of [Na ϩ ] in the cerebrospinal fluid (CSF) and, thus, the central nervous system is crucial for normal functioning of neurons. An increase in CSF [Na ϩ ] by as little as 2 mmol/L can increase the firing rate of neurons. 1,2 A chronic 5-mmol/L increase in CSF [Na ϩ ] causes sympathetic hyperactivity and hypertension. 3 Such a subtle increase in CSF [Na ϩ ] might be a primary abnormality in salt-induced hypertension. CSF [Na ϩ ] increases by Յ5 mmol/L in Dahl salt-sensitive (S) rats and spontaneously hypertensive rats on a high-salt diet, and this increase appears to precede the increase in blood pressure, whereas CSF [Na ϩ ] shows minimal changes in "salt-resistant" strains, such as Wistar-Kyoto and Dahl salt-resistant (R) rats. 3,4 The epithelium of the choroid plexus (CP) is the major site for production of CSF, which is later absorbed by arachnoid granulations. 5,6 Net transport of Na ϩ between plasma and CSF is a balance of Na ϩ influx into and efflux out of the CP cells, which is accomplished by selective distribution and activity of a variety of enzymes and transporters. 7,8 An increase in CSF [Na ϩ ] in Dahl S rats on a high-salt diet may, thus, be attributed to an increased efflux of Na ϩ into the CSF, decreased reuptake of Na ϩ from the CSF, or both. However, the actual mechanisms contributing to the increase in CSF [Na ϩ ] in Dahl S rats or spontaneously hypertensive rats on a high-salt diet have not yet been studied.MA number of Na ϩ transporters mediate Na ϩ influx into the CP. On the basis of their distribution either on the apical or the basolateral surface, they contribute to the transport of Na ϩ from CSF or plasma into the CP cells along a prevailing electrochemical gradient. The Na ϩ channel blocker, amiloride, decreases Na ϩ transport into the CP and CSF. 9 -11 Blockade of the sodium hydrogen exchanger (NHE) was first thought to be responsible for this, but NHE proteins are almost undetectable in the CP of rats. 5,12 Amiloride also blocks epithelial sodium channels (ENaCs), which we reported recently to be present in the CP of rats. 13 ENaCs are members of the amiloride-sensitive Na ϩ channels with 3 subunits, ␣, ␤, and ␥, forming a ...

Epithelial Na+ sodium channels in magnocellular cells of the rat supraoptic and paraventricular nuclei

“…In addition, immunoreactivity was found in cuboidal epithelium of the choroid plexus and in the ventricular ependyma. Overall, the localization of ␣-, ␤-, and ␥-ENaC subunits within the rat hypothalamus was similar to previous reports (3,4). Here, we report a more detailed localization of ␣-, ␤-, and ␥-ENaC within the SON and PVN performed by confocal double immunocytochemistry, using specific antibodies against ENaC subunits and antibodies against VP-or OT-NP.…”

“…Therefore, without quantitative RT-PCR it is only appropriate to state here that these dissociated cells are confirmed as MNCs producing OT or VP. Of these MNCs, mRNA for ␣-ENaC was found in cells 1, 2, 4, and 5, mRNA for ␤-ENaC was found in cells 1 and 3, mRNA for ␥-ENaC was found in cells 5, 9, 10, and 11, and mRNA for MR was found in cells 1,3,5,6,10, and 11. In addition, cell 12, although it did not contain VP or OT mRNA, contained ␣-ENaC, ␥-ENaC, and MR.…”

Aldosterone is synthesized in and activates bulbospinal neurons through mineralocorticoid receptors and ENaCs in the RVLM

“…22,34,35 Wang et al 36 showed the presence of ENaC in the choroid plexus and the ependyma of the anteroventral third ventricle, and reported that intracerebroventricular infusion of aldosterone increased blood pressure and intracerebroventricular infusion of benzamil blocked this increase. To our knowledge, there are no reports that have indicated the existence of ENaCs in bulbospinal RVLM neurons.…”

Cerebrospinal fluid hypersecretion in pediatric hydrocephalus

“…2,44 Several studies that inhibited Na + /K + -ATPase with ouabain on the luminal side of the CPE found a decrease in CSF produc- A small contribution to luminal Na + extrusion is made by NBCe2, which cotransports HCO 3 -. The K-Cl -cotransporter, KCC4, a genetic relative of the bumetanide-sensitive Na + -K + -2Cl -cotransporter, NKCC1 (see below), which is inhibited by furosemide, secretes the majority of Cl -into the CSF lumen.…”