Figure 3.

Nitric oxide (NO)/cGMP/PKG-I signaling pathway. In response to humoral or mechanical stimuli (e.g., Ach or shear stress), NO is synthesized in EC from L-arginine by activated form of eNOS. NO diffuses to neighboring SMC, where it activates soluble guanylate cyclase (sGC), which subsequently increases the intracellular production of cGMP from GTP. cGMP activates cGMP-dependent protein kinase I (PKG-I), which reduces intracellular Ca²⁺ concentration, and activates myosin light chain phosphatase (MLCP) to dephosphorylate myosin light chain (M), leading to SMC vasorelaxation. EC-derived NO can buffer ROS and prevent oxidative stress by inhibiting NOX activation in EC and SMC. It may also inhibit mitochondrial K_ATP channel (mitoK_ATP) opening, and consequently PTP opening, thus preventing the oxidative stress caused by mitochondrial ROS release.