Nitric oxide synthase-nitric oxide-cyclic guanosine monophosphate (NOS-NO-cGMP) pathway (NOS-NO-cGMP)

The Nitric oxide synthase-nitric oxide-cyclic guanosine monophosphate (NOS-NO-cGMP) pathway is a primary signaling mechanism regulating vascular tone and homeostasis (StatPearls, 2023). It begins with the production of nitric oxide (NO) from L-arginine by the enzyme nitric oxide synthase (NOS) (NCBI, 2021). NO then diffuses into smooth muscle cells to activate soluble guanylate cyclase (sGC), which converts GTP into cyclic guanosine monophosphate (cGMP) (PubMed, 2022). This second messenger, cGMP, activates protein kinase G (PKG), leading to reduced intracellular calcium and subsequent muscle relaxation (Nature Reviews Cardiology, 2019). Dysregulation of this pathway is a key factor in diseases such as pulmonary arterial hypertension, erectile dysfunction, and chronic heart failure (NIH, 2023). Pharmacological agents target various steps of this cascade, including NO donors like nitroglycerin and sGC stimulators like riociguat (PubChem, 2024). Additionally, phosphodiesterase-5 (PDE5) inhibitors like sildenafil are used to prolong cGMP activity by preventing its degradation (FDA, 2023). Therapeutic modulation of this pathway is highly effective but requires careful management to avoid systemic hypotension and adverse drug-drug interactions (AHA, 2022).

Other names

NO/cGMP signaling pathwayNitric oxide signaling cascadeL-arginine-NO-cGMP pathwayNitric oxide-guanylate cyclase-cGMP pathway

Stimulation of soluble guanylate cyclase, inhibition of phosphodiesterase-5, and provision of exogenous nitric oxide to increase intracellular cGMP levels and activate protein kinase G.