Nitric Oxide

Nitric oxide is a free-radical gas synthesised from L-arginine and oxygen by three nitric oxide synthase isoforms: neuronal, inducible and endothelial. It is not stored in vesicles; it diffuses from where it is made and survives only seconds before being scavenged by haemoglobin or oxidised. Its classical action is to enter smooth muscle, activate soluble guanylate cyclase, raise cyclic GMP and relax the vessel. The inducible isoform instead produces far larger amounts over hours as an antimicrobial and inflammatory effector.

The pharmacology is old and well characterised. Nitroglycerin has been used as a nitric oxide donor since the nineteenth century, long before the mechanism was known, and the identification of endothelium-derived relaxing factor as nitric oxide won the 1998 Nobel Prize. Sildenafil works downstream by inhibiting the phosphodiesterase that degrades cyclic GMP, and inhaled nitric oxide is approved for persistent pulmonary hypertension of the newborn. The cautionary result came from septic shock, where blocking nitric oxide synthase raised blood pressure as intended and increased mortality.

Isoform and location decide the effect, which is why blanket statements about more nitric oxide being better fail. Endothelial output supports perfusion and angiogenesis, and wound healing is impaired in mice lacking that isoform, while sustained inducible output in inflamed tissue generates peroxynitrite and damages matrix.

The marketing error is the nitric oxide booster. Plasma arginine is not normally rate-limiting for the endothelial enzyme, so oral loading has produced inconsistent haemodynamic effects, and a transient rise in muscle blood flow is not tissue growth or tendon repair. Claims that a repair peptide works through nitric oxide rest on rodent models, not on human measurement.