There are two general pathways that explain EDH
* Diffusible factors are endothelium-derived substances that are able to pass through internal elastic layer (IEL), reach underlying vascular smooth muscle cells at a concentration sufficient to activate ion channels, and initiate smooth muscle hyperpolarization and relaxation.
* Contact-mediated mechanisms bestow endothelial hyperpolarization that passively spreads to the smooth muscle through inter-cellular coupling, and, therefore, EDH is considered as a solely electrical event.