The MEJ facilitates communication between vascular ECs and smooth muscle cells to regulate vascular tone. Upon adrenergic stimulation of vascular smooth muscle, inositol triphosphate (IP3) generated by phospholipase C diffuses into ECs via gap junctions and triggers release of Ca²⁺ from the endoplasmic reticulum. Cytosolic Ca²⁺-mediated signaling leads to phosphorylation and activation of eNOS, which catalyzes the production of NO from L-arginine. NO diffuses through the MEJ into smooth muscle cells and activates guanylate cyclase, leading to an increase in cyclic guanosine monophosphate (cGMP), causing smooth muscle relaxation and vasodilation. EC α-globin can bind and degrade NO to limit its bioavailability. The figure was created using BioRender.