Our study and the investigation by Zhang et al. used metformin at the following doses: 200 mg/kg/day intravenously and a daily dose of 300–350 mg/kg in drinking water, respectively. Metformin is usually used in rats in the 100–300 mg/kg/day range orally or intravenously (Santuré et al., 2000; Choi et al., 2008). In patients with type-2 diabetes, the oral form of metformin is usually given at total doses of 500–2,000 mg daily (Stumvoll et al., 1995; Basu et al., 2008; Takahara et al., 2012). Interestingly, Santuré and colleagues found that 3 weeks of treatment with metformin improves the glucose disposal in SHRs but has no blood pressure-lowering effect and no influence on vascular responses to insulin. In another study, 25–200 μg/day intracerebroventricular administration of metformin to SHRs attenuated 8% NaCl diet-induced hypertension; 100–200 mg/kg doses were highly neurotoxic as demonstrated by a histological evaluation post-mortem (Petersen et al., 2001). Together, these considerations and findings suggest that the selection of experimental model, route of administration, and dosage may all be critical for studying the effects of AMPK activators on blood pressure.