Nitric Oxide (NO)
A small signalling molecule produced by nitric oxide synthase enzymes that plays critical roles in vasodilation, immune defence, neurotransmission, and tissue repair. Nitric oxide modulation is a proposed mechanism of action for several tissue repair research peptides and is important in angiogenesis and wound healing.
Technical Context
NO is produced by three nitric oxide synthase isoforms: nNOS/NOS1 (neuronal — neuromodulation), iNOS/NOS2 (inducible — produced by macrophages during inflammation, killing pathogens via high NO concentrations), and eNOS/NOS3 (endothelial — producing low-level NO for vasodilation and endothelial homeostasis). The reaction: L-arginine + O2 → L-citrulline + NO (requiring BH4, NADPH as cofactors). NO activates soluble guanylyl cyclase → cGMP → PKG → smooth muscle relaxation (vasodilation). In wound healing, NO modulates: inflammation (regulating macrophage and neutrophil activity), angiogenesis (stimulating VEGF expression and endothelial cell migration), collagen deposition (stimulating fibroblast collagen synthesis at low concentrations), and antimicrobial defence (high concentrations from iNOS kill bacteria). Several research peptides are proposed to work through NO pathway modulation. Vosoritide's downstream signalling also involves cGMP (via particulate guanylyl cyclase NPR-B rather than soluble guanylyl cyclase).