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Am J Physiol Regul Integr Comp Physiol. 2012 Jul 15;303(2):R236-45. doi: 10.1152/ajpregu.00381.2011. Epub 2012 May 30.

Possible role of brain salt-inducible kinase 1 in responses to central sodium in Dahl rats.

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Hypertension Unit, University of Ottawa Heart Institute, Ottawa, Ontario, Canada.


In Dahl salt-sensitive (S) rats, Na(+) entry into the cerebrospinal fluid (CSF) and sympathoexcitatory and pressor responses to CSF Na(+) are enhanced. Salt-inducible kinase 1 (SIK1) increases Na(+)/K(+)-ATPase activity in kidney cells. We tested the possible role of SIK1 in regulation of CSF [Na(+)] and responses to Na(+) in the brain. SIK1 protein and activity were lower in hypothalamic tissue of Dahl S (SS/Mcw) compared with salt-resistant SS.BN13 rats. Intracerebroventricular infusion of the protein kinase inhibitor staurosporine at 25 ng/day, to inhibit SIK1 further increased mean arterial pressure (MAP) and HR but did not affect the increase in CSF [Na(+)] or hypothalamic aldosterone in Dahl S on a high-salt diet. Intracerebroventricular infusion of Na(+)-rich artificial CSF caused significantly larger increases in renal sympathetic nerve activity, MAP, and HR in Dahl S vs. SS.BN13 or Wistar rats on a normal-salt diet. Intracerebroventricular injection of 5 ng staurosporine enhanced these responses, but the enhancement in Dahl S rats was only one-third that in SS.BN13 and Wistar rats. Staurosporine had no effect on MAP and HR responses to intracerebroventricular ANG II or carbachol, whereas the specific protein kinase C inhibitor GF109203X inhibited pressor responses to intracerebroventricular Na(+)-rich artificial CSF or ANG II. These results suggest that the SIK1-Na(+)/K(+)-ATPase network in neurons acts to attenuate sympathoexcitatory and pressor responses to increases in brain [Na(+)]. The lower hypothalamic SIK1 activity and smaller effect of staurosporine in Dahl S rats suggest that impaired activation of neuronal SIK1 by Na(+) may contribute to their enhanced central responses to sodium.

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