Abstract 422: Role of Brain Salt-inducible Kinase 1 in Responses to Central Sodium in Salt-induced Hypertension
In Dahl salt sensitive (S) rats, sympatho-excitatory 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 sympatho-excitatory and pressor responses to Na+ in the brain. Icv injection of the protein kinase inhibitor staurosporine (staur, 5ng) to inhibit SIK1 similarly enhanced renal sympathetic nerve activity (RSNA), BP and HR responses to icv infusion of Na+-rich aCSF in Wistar and salt-resistant Dahl SS.BN13. The enhancement in Dahl S rats was only 1/3 of that in other strains. Staur had no effect on BP responses to icv Ang II or carbachol, whereas the specific protein kinase C inhibitor GF109203X attenuated pressor responses to icv Na+-rich aCSF or Ang II. Hypothalamic SIK1 protein and activity, measured by Western blot and phosphocellulose binding technique, were lower in Dahl S vs SS.BN13 rats after high salt diet for 2 weeks. Staur at 5-50 nM inhibited SIK1 activity in a dose-related manner. These data suggest that the SIK1 -Na+/K+-ATPase network in neurons acts as a feedback mechanism to attenuate sympatho-excitatory and pressor responses to increases in brain [Na+]. Lower neuronal SIK1 protein expression and activity in Dahl S rats may contribute to enhanced responses to CSF Na+ and thereby to their salt-induced hypertension. Data= means±SE (n=4-7). * p<0.05, vs. SS.BN13 or Wistar rats.
- © 2012 by American Heart Association, Inc.