NO: the Miracle Molecule

Nitric oxide (NO) is an endogenous gas molecule, produced by arginine (L-Argnine) and catalyzed by nitric oxide synthase (NOS). It is widely present in the human body and participates in various physiological processes. As a "miracle molecule", NO has been indirectly used in medicine as a cardiovascular specific drug for nearly a century, and was later found to be an important signaling molecule in the human body.

In 1998, a major breakthrough was made in the research on the mechanism of NO gas molecules to dilate blood vessels, and the research won the Nobel Prize. In the following years, clinical research has successively revealed the relevant mechanism of NO as an endogenous gas signal molecule, and confirmed that NO can dilate blood vessels in the human body. It plays an important role in anti-infection, stimulating soft tissue regeneration, and regulating immunity. The mechanism by which NO participates in the regulation of human physiological processes has been widely used in clinical practice. In recent years, its effectiveness and safety in the treatment of acute and severe pulmonary hypertension and respiratory failure have been highly recognized by clinical experts from home and abroad, and clinical diagnosis and treatment guidelines have been widely formed. The mechanisms of action of NO that have been extensively validated by basic medical research include:

• Vasodilation: The main physiological function of NO is to relax the vascular endothelium, which regulates blood flow, velocity and vascular resistance under physiological conditions. NO activates soluble guanylate cyclase (sGC) in smooth muscle cells, which increases the content of intracellular cGMP; the increased cGMP causes phosphorylation of various proteins through protein kinase G, which reduces the concentration of intracellular calcium, thereby causing vasodilatation.

• Anti-microbial effect: As a highly active molecule, NO is a free radical, which is very easy to participate in electron reactions and join the redox process of the body. NO can nitrosate membrane proteins extracellularly, leading to inactivation of membrane proteins and destroying the structure of cell membranes; it generates free radicals in cells, leading to the DNA fragmentation of microbial cells, so it can kill a variety of bacteria, fungi and pathogens that infect cells.

• Wound healing effect: The role of NO in promoting wound healing has been widely verified, and its related mechanisms include: NO inhibits the activity of neutrophils, monocytes and macrophages, facilitates the infiltration of neutrophils, and separates the necrotic tissue and the normal tissue, creating conditions for wound repair; NO can dilate blood vessels, thereby regulating the caliber and flow of blood vessels, providing sufficient blood supply for granulation tissue, which is conducive to the growth of new blood vessels; NO can regulate inflammation, inhibit edema formation and granulomas caused by cellular exudation; NO promotes the movement of keratinocytes, which in turn promotes wound healing.

• Neuromodulation: Studies on the L-Arg → NO pathway in the central nervous system (CNS) suggest that NO acts on adjacent peripheral neurons such as pre-prominent nerve endings and astrocytes through diffusion, and then activates GCs, thereby increasing the level of cGMP levels and producing physiological effects. The L-Arg → NO pathway also exists in the peripheral nervous system. NO is considered to be a non-cholinergic, non-adrenergic neurotransmitter or mediator, involved in the process of pain afferent and sensory transmission.