FIGURE 2.

The NO–cGMP signalling pathway in the vasculature. The figure shows the generator cells, for example, vascular endothelial cells, the target cells, for example, vascular smooth muscle cells and biochemical processes involved in NO signalling in the vasculature. NO is produced through the conversion of the substrate l‐arginine to l‐citrulline by endothelial NO synthase (NOS3) in vascular endothelial cells. Subsequently, NO diffuses to neighbouring vascular smooth muscle cells where it activates soluble GC (sGC), which converts guanosine triphosphate (GTP) to cGMP. cGMP is a secondary messenger enacting cellular processes through the regulation of protein‐dependent kinases, for example, PKG, and cGMP‐gated ion channels. The cellular actions of cGMP can be prolonged by PDE type 5 inhibitors (PDE5Is), which prevent its degradation by PDE type 5 (PDE5), resulting in vasodilatory, antioxidative and anti‐proliferative effects in several organ systems and diseases. Icons with permission from ^© iStock.com/Alex Doubovitsky