Salt‐sensitive hypertension is associated with reduced urea transporter B expression in the choroid plexus and increased Na+ concentration in the cerebrospinal fluid

Abstract

High salt intake causes an increase in Na+ concentration in the CSF of SHR and Dahl S rats, and increased CSF [Na+] contributes to sympothoexcitation and hypertension. However, the transporters in the choroid plexus (CP) mediating the imbalance of water and electrolytes in the CSF are still not identified. Current study demonstrated that high salt intake did not alter UT‐A expression, but there was a significant reduction in UT‐B expression in the CP of Dahl S rats. Reduced UT‐B expression was associated with increased [Na+] in the CSF and elevated MAP, as measured with radiotelemetry in Dahl S rats treated with high salt diet. We next examined the effect of selectively silencing UT‐B in the CP on CSF [Na+] and MAP in normotensive rats on normal diet versus high salt diet. ICV injection of lentiviral vector containing UT‐B shRNA (Lv‐UTB‐shRNA) significantly reduced UT‐B expression in the CP of rats as compared with rats received scramble Lv‐SCR‐shRNA ICV injection. High salt diet significantly increased MAP and HR in rats received ICV injection of Lv‐UTB‐shRNA. The elevated MAP was associated with increased [Na+] in the CSF. Chronic ICV infusion of Na+‐rich CSF resulted in significant elevations in MAP and HR. In conclusion, high salt diet significantly reduced UT‐B expression in the CP of Dahl S rats and selective silencing of UT‐B expression in the CP of normotensive rats markedly increases salt‐sensitivity in MAP and CSF [Na+]. These data indicate that reduced UT‐B expression in the CP may contribute to an imbalance of water and electrolytes in the CSF of Dahl S rats on high salt diet, thereby contributing to the development of salt‐sensitive hypertension.