The renal effects of AMPK activators have been characterized in less detail than in such systems as skeletal and cardiac muscle or gastrointestinal tract. In our study, we have not observed effects of AICAR infusion on renal salt handling during BP elevation, although high-salt intake itself activated the AMPK pathway even without AICAR treatment, as discussed above. Another factor that could contribute to the observed lack of effect of the AMPK activators on BP might be that the dose was insufficient to target the kidneys. However, 200 mg/kg/day metformin did induce hepatic effects, which suggests the physiological efficacy of this infusion. AICAR is often used at high doses: antidiabetic effects are exhibited at doses of ~1 g/kg/day intravenously in humans (Boon et al., 2008) and rodents (Minokoshi et al., 2002). The safety and kinetics study in healthy men demonstrated that AICAR is poorly bioavailable (< 5%) when administered orally in solution; after intravenous injection the elimination phase half-time (t1/2β) was 1.4 h (Dixon et al., 1991). Our much lower intravenous dose of 20 mg/kg/day administration of AICAR did not exert any effects.