Considering the lack of effect of metformin on blood pressure elevation in Dahl SS rats, we tested whether another AMPK-activating pharmacological agent, AICAR, attenuates high blood pressure. Similarly, we found that 20 mg/kg/day continuous AICAR administration had no effect on the development of hypertension (Figure 5A). Analysis of the plasma samples collected via arterial catheters revealed that both vehicle- and AICAR-infused animals were euglycemic during the experiment (Figure 5B). By the end of the study, both groups demonstrated significant proteinuria, and neither sodium, potassium, total urine (73 ± 1.2 vs. 72.5 ± 8.4 ml/day) excretion, nor total body weight (288.4 ± 14.7 vs. 306 ± 7.3 g) differed between the two groups (Figures 5C–E). Histological analysis revealed massive abundance of protein casts, indicating kidney damage in the renal tissues in both groups (Figure 6A). The abundances of p-ACC, pThr172-AMPKα and total AMPKα, markers of AMPK pathway activity, in the cortex of AICAR-treated animals were similar to those of the control group as tested by Western blotting (Figure 6B).