Xe activates HIF in the mouse kidney in vivo and in cultured HK2 cells. Mice were exposed to 70% N2, 70% Xe, and 70% N2O, for 2 h. As a positive control for HIF activation, mice were exposed to 8% O2. Renal cortices were harvested for immunoblot from 0 to 24 h after treatments. (A) Xe significantly increased HIF-1α expression from 2 h after exposure (n = 5 to 6 at each time point) compared with N2 control. (B) Xe significantly increased EPO expression (n = 5 to 6) 24 h after exposure compared with N2 (control). (C) Xe significantly increased expression VEGF expression (n = 5 to 6) from 8 h after exposure compared with N2 control. (D) Exposure to the anesthetic gas, N2O, did not affect HIF-1α expression (n = 4). (E) Effect of hypoxia on HIF-1α expression (n = 5) was NS ≥2 h after exposure compared with N2 control. (F) Xe significantly increases HIF-1α expression from 8 h after exposure (n = 4 at each time point) compared with N2 control in HK2 cell line. Data are means ± SD. C, control. *P < 0.05, **P < 0.01 versus control.