AMPK activators have proven themselves to be useful drugs for metabolic disorders, including those associated with high blood pressure. Recently, Lazo-Fernández and colleagues determined that systemic knockout of α1 combined with kidney epithelium-specific deletion of α2 AMPK subunits led to a water and salt wasting phenotype in mice. The authors also suggested that activity of NKCC2, which serves as a substrate for phosphorylation by AMPK, might be reduced with AMPK targeting (Lazo-Fernández et al., 2017). Another example of the effect of AMPK on the renal concentrating ability in normal animals comes from experiments on kidney slices isolated from Sprague Dawley rats where AICAR treatment decreased apical membrane localization of AQP2, which could have a diluting effect on urine (Al-Bataineh et al., 2016). The current study was aimed at investigating the prospect of targeting AMPK for the treatment of salt-sensitive hypertension. Earlier, it was shown with a precise servo-control of body fluid volume that fluid retention is required to trigger the rise of pressure in Dahl SS rats (Greene et al., 1990).