AMP-activated protein kinase (AMPK) and diphosphoglycerate (BPG) mutase activities are induced by angiotensin II (Ang II) in EpoR-Cre+ mice but not in Ang II–infused Adora2bf/f/EpoR-Cre+ mice, and AICAR (5-aminoimidazole-4-carboxamide ribonucleotide) treatment rescues the CKD phenotype in Adora2bf/f/EpoR-Cre+ mice. (A–C) Phosphorylation levels of erythrocyte AMPK, mutase activity, and 2,3-BPG levels in mice at day 14 with Ang II or PBS infusion. Data are expressed as mean ± SEM. n=4 for each group. *P<0.05. (D and E) AICAR treatment prevented renal hypoxia. (D) Immunohistochemical analysis of tissue hypoxia by Hypoxyprobe in the kidney. Scale bar, 70 μm. (E) Quantitative image analyses of tissue hypoxia by Hypoxyprobe in kidney. n=4 for each group. *P<0.05. (F) Ratio of microalbunin to creatinine in 24 hour urine. n=4 or 8 for each group. *P<0.05. (G and H) Preproendothelin-1 (prepro-ET1), endothelin receptor A (EDNRA), Collagen I, and Fibronectin mRNA levels in mouse kidney. Data are expressed as mean ± SEM. n=3–7 for each group. *P<0.05. (I) BP in mice. Data are expressed as mean ± SEM. n=4 for each group.