FIGURE 1.

Drug targets in the nitric oxide signaling pathway. By the conventional pathway, endothelial nitric oxide synthase (eNOS) produces nitric oxide—which may also be pharmacologically supplemented by nitrate or nitrite—in endothelial cells from substrates, l-arginine and oxygen. Nitric oxide diffuses to neighboring vascular smooth muscle or cardiac myocytes and binds its receptor, soluble guanylyl cyclase (sGC), to produce cyclic guanosine monophosphate (cGMP). cGMP activates protein kinase G (PKG), promoting signaling involved in smooth muscle relaxation and cardiac compliance and suppressing hypertrophic signaling in cardiac myocytes. To boost cGMP levels, sGC stimulators can be used as well as inhibitors of phosphodiesterase 5 (PDE5), which negatively regulates nitric oxide signaling by degrading cGMP. Figure produced using BioRender.com.