We recently demonstrated that high ENaC activity contributes to the development of hypertension in Dahl SS rats (Pavlov et al., 2013). We and others have shown that the AMPK pathway regulates ENaC activity in cultured cells and in vivo (Carattino et al., 2005; Almaça et al., 2009; Myerburg et al., 2010), although it is unclear whether this mechanism is functional in the Dahl SS rats. Therefore, here we studied whether the AMPK activator metformin has an effect on the activity of ENaC in the experiments described above in this important animal model of hypertension. CCDs were manually isolated immediately after organ collection, and patch-clamp analysis was performed on split-open tubules to assess channel activity. Figure 4A demonstrates representative ENaC current traces recorded from the apical membrane of vehicle- and metformin-treated Dahl SS rats. The analysis did not reveal any significant differences in total ENaC activity (NPo), open probability of individual channels (Po) or the number of channels (N) observed in patches (Figure 4B). Therefore, in this rat model of hypertension, metformin treatment does not decrease ENaC activity.