Genetic Determinants Defined By Two Congenic Strains Of Dahl Salt‐Sensitive (S) Rats Are Distinguishable In Their Neuronal Responsiveness To Central Na+

In Dahl S rats, enhanced Na + transport via aldosterone‐MR‐ENaC‐“ouabain” may contribute to increased Na + entry from blood into CNS and increased sympathetic responses to brain Na + . We assessed these 2 phenotypes in Lewis, Dahl S rats and two congenic substrains C10S.L16 and C17S.L2. On high salt, C10S.L16 and C17S.L2 exhibit similar CSF [Na + ]↑ but lower BP versus Dahl S rats. Only C10S.L16 showed attenuated sympathetic and pressor responses to acute and chronic icv infusion of Na + ‐rich aCSF.In Dahl S rats on high salt, hypertension was prevented by icv infusions of Na + channel blocker benzamil or MR blocker spironolactone, but CSF [Na + ]↑ was prevented only by benzamil. Thus in Dahl S rats genetic variants within the segment of Ch10 but not 17 may contribute to gain‐of‐function of central mechanisms determining neuronal excitability to CSF Na + . Increased Na + entry into the CSF and enhanced sympathetic responses to brain Na + are likely due to different genetic variants in e.g. components of aldosterone‐MR‐ENaC‐“ouabain”.