Synthesis and signaling of PGs in the vascular system. Upon stimulation, AA is released from the endothelial cell membrane to the cytosol where it is enzymatically converted to PGH₂ by COX1 and COX2. Subsequently, PGH₂ is transformed to PGI₂, PGE₂, PGD₂, PGF_2α, and TxA₂. These substances, as well as untransformed PGH₂, are released out of endothelial cells and into the circulation, where they interact with their receptors localized on the smooth muscle cell surface and trigger vasoactive signals.