New paradigm for EPO-induced NO. Currently, it is thought that EPO induction of NO is secondary to downstream signaling of the homodimeric EPO receptor via Akt. In addition, it is thought that EPO stimulation of the EPO receptor can lead to an increase in VEGF that can bind to VEGF-R2 also leading to NO expression. We propose that it is the heterodimeric EPO receptor (composed of the βC-R and EPO receptor) that is responsible for NO stimulation. In addition, the βC-R forms a complex with VEGF-R2, and this interaction is critical for stimulation of NO not only by the heterodimeric EPO receptor but also for VEGF-R2.