Nitric oxide pathway components (NO pathway)

The nitric oxide (NO) pathway is a fundamental signaling cascade responsible for regulating vascular tone, platelet aggregation, and neuronal communication (StatPearls, 2023). It is initiated by nitric oxide synthases (NOS), which catalyze the production of NO from L-arginine (UniProt, 2023). Once produced, NO diffuses into target cells and binds to soluble guanylate cyclase (sGC), triggering the synthesis of cyclic guanosine monophosphate (cGMP), which mediates smooth muscle relaxation and other physiological effects (PubMed, PMC2806014). Impairment of this pathway is a hallmark of endothelial dysfunction and contributes to diseases such as hypertension, heart failure, and pulmonary arterial hypertension (NIH, 2022). Therapeutic strategies often focus on restoring NO signaling through the use of exogenous NO donors, sGC stimulators like riociguat, or phosphodiesterase-5 (PDE5) inhibitors like sildenafil (DrugBank, 2024). While highly effective, these therapies require careful management due to the risk of profound hypotension and complex interactions between different classes of pathway modulators (FDA, 2023).

Other names

Nitric oxide signaling pathwayNO-sGC-cGMP pathwayL-arginine-nitric oxide pathway

Drugs targeting this pathway function by increasing the bioavailability of nitric oxide through NO donors, directly stimulating or activating soluble guanylate cyclase (sGC stimulators/activators), or inhibiting the degradation of the downstream messenger cGMP via PDE5 inhibitors (StatPearls, 2023; DrugBank, 2024).