Endothelial nitric oxide-dependent vasodilation pathway (NO-sGC-cGMP pathway) (NO-sGC-cGMP pathway)

The endothelial nitric oxide-dependent vasodilation pathway is a fundamental signaling cascade that regulates vascular tone and systemic blood pressure (StatPearls, 2023). It is initiated by the enzyme endothelial nitric oxide synthase (eNOS), which converts L-arginine into nitric oxide (NO) in response to mechanical shear stress or agonists like acetylcholine (UniProt, P29474). NO then diffuses into vascular smooth muscle cells to activate soluble guanylate cyclase (sGC), increasing the production of cyclic guanosine monophosphate (cGMP) (Nature Reviews Cardiology, 2019). Elevated cGMP levels activate protein kinase G, leading to reduced intracellular calcium and subsequent vasorelaxation. Impairment of this pathway, known as endothelial dysfunction, is a primary driver of cardiovascular conditions including hypertension and atherosclerosis (PubMed, 28438794). Therapeutic strategies targeting this pathway include NO donors like nitroglycerin, sGC stimulators such as riociguat, and PDE5 inhibitors like sildenafil, which prevent cGMP degradation (PubChem, CID 5212).

Other names

Nitric oxide-cGMP signaling pathwayeNOS-sGC-cGMP pathwayEndothelium-dependent vasorelaxationNitric oxide-mediated vasodilation

The pathway is modulated by increasing nitric oxide availability (NO donors), stimulating soluble guanylate cyclase directly (sGC stimulators), or inhibiting phosphodiesterase-5 (PDE5 inhibitors) to prevent the degradation of cyclic guanosine monophosphate, all of which lead to vascular smooth muscle relaxation (Nature Reviews Cardiology, 2019).