Nitric oxide–cyclic guanosine monophosphate signaling pathway (NO–cGMP pathway)

The nitric oxide–cyclic guanosine monophosphate signaling pathway is a fundamental cellular communication system involved in diverse physiological processes such as vascular tone regulation, neurotransmission, inhibition of platelet aggregation, and cardiac function. The core sequence involves synthesis of nitric oxide by nitric oxide synthases from L‐arginine; NO then diffuses into adjacent cells where it binds to and activates soluble guanylyl cyclase. This enzyme catalyzes conversion of GTP into cyclic GMP—a second messenger that activates protein kinase G and other effectors—leading ultimately to smooth muscle relaxation among other effects. Dysregulation at any step can contribute to diseases including cardiovascular disorders like heart failure and pulmonary hypertension. Pharmacological agents exploit various nodes within this cascade for therapeutic benefit—most notably through inhibition of phosphodiesterases that degrade cGMP or direct stimulation/activation of sGC—but these interventions carry risks such as hypotension due to systemic vasodilation[1][2][7].

Other names

NO–cGMP signalingNitric oxide/cGMP pathwayNitric oxide signaling cascade

Mechanisms depend on the component targeted; examples include: Inhibition of cGMP degradation by blocking PDE5 → increased cGMP levels → smooth muscle relaxation. Direct stimulation or activation of soluble guanylyl cyclase → increased cGMP synthesis. Exogenous delivery of nitric oxide donors to activate sGC and increase cGMP production.