Sodium Transport in the Choroid Plexus and Salt-Sensitive Hypertension

To elucidate the role of epithelial sodium channels (ENaCs) and Na+-K+-ATPase in Na+ transport by the choroid plexus, we studied ENaC expression and Na+ 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+-K+-ATPase blocker ouabain on sodium transport were evaluated by measuring the amounts of retained Na-22(+) and by evaluating intracellular [Na+] 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(-8) M) decreased Na-22(+) retention by 20% and ouabain (10(-3) M) increased retention by 40%, whereas ouabain and benzamil combined caused no change. Similar changes were noted in intracellular [Na+]. In Dahl rats on a regular salt diet, intracellular [Na+] was similar, but the amount of retained Na-22(+) was less in sensitive versus resistant rats. High salt did not affect ENaC mRNA or protein, nor the benzamil induced decreases in retained Na-22(+) or intracellular [Na+] in either strain. However, high salt increased intracellular [Na+] and attenuated the increase in uptake of Na-22(+) by ouabain in resistant but not sensitive rats, suggesting a decrease in Na+-K+-ATPase activity only in resistant rats. These findings suggest that both ENaC and Na+-K+-ATPase regulate Na+ transport in the choroid plexus. Aberrant regulation of Na+ transport and of Na+-K+-ATPase activity, but not of ENaCs, might contribute to the increase in cerebrospinal fluid [Na+] in Dahl salt-sensitive rats on a high-salt diet. (Hypertension. 2009; 54: 860-867.)