Fig. 1.

Physiologic vasorelaxation by NO, CO, and H₂S. Stimulation of muscarinic acetylcholine receptors (AChRs) on endothelial cells activates Ca²⁺-calmodulin (CaM), which in turn binds to and stimulates endothelial NO synthase (eNOS), cystathionine γ-lyase (CSE), and HO2 to produce NO, H₂S, and CO, respectively. NO and CO diffuse into the adjacent smooth muscle cells and activate soluble guanylyl cyclase (sGC) to produce cyclic GMP (cGMP), ultimately affecting the actin-myosin cross-bridge. H₂S also diffuses into smooth muscle cells, where it likely activates K⁺ channels. These actions of all three gases lead to vasorelaxation.