Figure 1. Endothelium-dependent vasodilation. Acetylcholine induces an increase in intracellular calcium concentration and leads to the production and release of nitric oxide (NO) and prostacyclin (PGI₂), in addition to the opening of potassium channels, which in turn induces vascular smooth muscle cell relaxation. NO diffuses to the underlying smooth muscle cell and induces relaxation by increasing the production of cGMP. Prostacyclin is the main prostanoid synthesized by vascular endothelium, and acts via the prostacyclin receptor (IP). The opening of intermediate conductance calcium-activated potassium channels (Kca3.1) and small conductance calcium-activated potassium channels (Kca2.3) in the endothelial cell induces vascular smooth muscle cell hyperpolarization, which is evoked by electrical coupling through the myoendothelial gap junctions.