RyR2 gene knockout blocked hypoxia-induced ROS generation in PASMCs and mitochondria. ROS generation, assessed using DCF (A), lucigenin (B), and Red CC-1 (C), in PASMCs from WT and RyR2 KO mice. ROS generation, examined using H2DCF/DA (DCF) (A), lucigenin (B), and Red CC-1 (C), in PASMCs from WT and RyR2 KO mice. ROS generation, assessed using DCF (D), lucigenin (E), and Red CC-1 (F), in isolated mitochondria from WT and RyR2 KO mouse PASMCs. Data were obtained from three separate experiments. *p < 0.05 compared with normoxic WT group, and #p < 0.05 compared with hypoxic WT group. KO, knockout; WT, wild type.