The transcription factor complex hypoxia-inducible factor 1 (HIF1) plays a crucial role in cellular adaptation to low oxygen availability. HIF prolyl hydroxylases (PHDs) act as oxygen sensors through posttranslational modification of the HIF-1 alpha subunit, which is sent to proteasomal degradation under normoxia. Reduced activity of PHDs under hypoxia allows HIF-1 alpha to accumulate. Herein we show that nitric oxide (NO) like hypoxia inhibited PHD activity and induced HIF-1 alpha accumulation under normoxia or, in addition to hypoxia, as long as NO was released into the cell culture system. In parallel PHD2 and PHD3 expression was increased in NO treated cells. Knock down of HIF-1 alpha by siRNA treatment revealed that the NO induced PHD2 and PHD3 expression was strictly HIF-1 alpha dependent. After induction of PHD enzymes NO treated cells displayed reduced hypoxic accumulation of HIF-1 alpha. Knock down of PHDs revealed that PHD2 was responsible for this effect. We conclude, that NO induced PHD2 expression delayes HIF-1 alpha accumulation in hypoxia. Consequently NO can interfere with O2-sensing through HIF-1 dependent induction of prolyl hydroxylase 2.