Salt-inducible kinases (SIKs) represent a subfamily of AMPK family kinases. SIK1 
has been shown to act as a mediator during the cellular adaptation to variations 
in intracellular sodium in a variety of cell types. SIK2, as an isoform of the 
SIK family, modulates various biological functions and acts as a signal 
transmitter in various pathways. To evaluate the role of both SIK1 and SIK2 
isoforms in blood pressure (BP), body fluid regulation and cardiac hypertrophy 
development, we made use of constitutive sik1-/- (SIK1-KO), sik2-/- (SIK2-KO), 
double sik1-/-sik2-/- (double SIK1*2-KO) knockout and wild-type (WT) mice 
challenged to a standard (0.3% NaCl) or chronic high-salt (HS, 8% NaCl) diet 
intake for 12 weeks.Mice, under a standard diet intake, had similar and normal 
BP. On a chronic HS intake, SIK1-KO and double SIK1*2-KO mice showed increased 
BP, but not WT and SIK2-KO mice. A chronic HS intake led to the development of 
cardiac left ventricle hypertrophy (LVH) in normotensive WT and hypertensive 
SIK1-KO mice, but not in SIK2-KO mice. Double SIK1*2-KO mice under standard diet 
intake show normal BP but an increased LV mass. Remarkably, in response to a 
dietary stress condition, there is an increase in BP but LVH remained unchanged 
in double SIK1*2-KO mice.In summary, SIK1 isoform is required for maintaining 
normal BP in response to HS intake. LVH triggered by HS intake requires SIK2 
isoform and is independent of high BP.