[2] Research into its function led to the 1998 Nobel Prize for elucidating the role of nitric oxide as a cardiovascular signalling molecule.

Platelet-derived factors, shear stress, acetylcholine, and cytokines stimulate the production of NO by endothelial nitric oxide synthase (eNOS).

Besides mediating normal functions, NO is implicated in pathophysiologic states as diverse as septic shock, hypertension, stroke, and neurodegenerative diseases.

Likewise, Sildenafil citrate, popularly known by the trade name Viagra, stimulates erections primarily by enhancing signaling through the nitric oxide pathway.

[10] When eaten and absorbed into the bloodstream, nitrate is concentrated in saliva (about 10-fold) and is reduced to nitrite on the surface of the tongue by a biofilm of commensal facultative anaerobic bacteria.

[11] This nitrite is swallowed and reacts with acid and reducing substances in the stomach (such as ascorbate) to produce high concentrations of nitric oxide.

[13] Nitrate-rich vegetables, in particular leafy greens, such as spinach and arugula, and beetroot, have been shown to increase cardioprotective levels of nitric oxide with a corresponding reduction in blood pressure in pre-hypertensive persons.

[17] Oral antiseptic mouthwash has been shown to eliminate the blood pressure lowering effects of dietary nitrate due to eradication of nitrate-reducing bacteria.

In alternative fashion, nitrite anions on sun-exposed skin may be photolyzed to free nitric oxide radicals by UVA in sunlight.

[38] The inducible pathway (iNOS) of nitrogen oxide synthesis in phagocytes can generate large amounts of NO that trigger apoptosis and kill other cells.

S-nitrosation involves the (reversible) conversion of thiol groups, including cysteine residues in proteins, to form S-nitrosothiols (RSNOs).

[45] NO has been demonstrated to activate NF-κB in peripheral blood mononuclear cells, a transcription factor in iNOS gene expression in response to inflammation.

[8] Also a neurotransmitter, nitric oxide acts in the nitrergic neurons active on smooth muscle, abundant in the gastrointestinal tract and erectile tissue.

Nitric oxide (NO) contributes to vessel homeostasis by inhibiting vascular smooth muscle contraction and growth, platelet aggregation, and leukocyte adhesion to the endothelium.

[64][65][66] Nitric oxide interactions have been found within signaling pathways of plant hormones such as auxin,[67] ethylene,[63][68][69] Abscisic acid[61] and cytokinin.

[70] Atmospheric nitric oxide can enter the stomates of most vascular species, and can have effects ranging from leaf blemishing, to stunting of growth, to necrosis.

In 2009 it was reported that nitric oxide plays an important role in this bacteria's recovery from radiation exposure: The gas is required for division and proliferation after DNA damage has been repaired.

In the European Union, nitric oxide in conjunction with ventilatory support and other appropriate active substances, is indicated:[74] In the United States, it is indicated to improve oxygenation and reduce the need for extracorporeal membrane oxygenation in term and near-term (>34 weeks gestation) neonates with hypoxic respiratory failure associated with clinical or echocardiographic evidence of pulmonary hypertension in conjunction with ventilatory support and other appropriate agents.

This is called PiNO (pulsed inhaled nitric oxide) and results in better matching of ventilation and perfusion and thereby improves the arterial oxygenation.

[citation needed] Inhaled nitric oxide is contraindicated in the treatment of neonates known to be dependent on right-to-left shunting of blood.

[citation needed] Nitric oxide production is associated with nonalcoholic fatty liver disease (NAFLD) and is essential for hepatic lipid metabolism under starvation.

Nitric oxide therapy has the potential to significantly increase the quality of life and, in some cases, save the lives of infants at risk for pulmonary vascular disease.

Vascular damage can lead to decreased blood flow to the extremities, causing the diabetic patient to be more likely to develop neuropathy and non-healing ulcers, and to be at a greater risk for lower limb amputation.

[citation needed] Nitric oxide is considered an antianginal drug: It causes vasodilation, which can help with ischemic pain, known as angina, by decreasing the cardiac workload.

In contrast, inhaled nitric oxide has been shown to help survival and recovery from paraquat poisoning, which produces lung tissue-damaging superoxide and hinders NOS metabolism.

There is a potential role for the use of nitric oxide in alleviating bladder contractile dysfunctions,[92][93] and recent evidence suggests that nitrates may be beneficial for treatment of angina due to reduced myocardial oxygen consumption both by decreasing preload and afterload and by some direct vasodilation of coronary vessels.

[99] Brian Strickland, MD, a fellow in Wilderness Medicine at Massachusetts General Hospital who studies "acute respiratory distress" in high altitudes, is applying this research towards COVID-19.

[102] This approach was inspired by the work of associate professor of emergency medicine at the Harvard Medical School N. Stuart Harris, who has been studying the effects of altitude sickness on mountain climbers, such as those who climb Mount Everest.

Harris noticed that the consequences of high level altitude sickness on the human body mirrored COVID-19's dysfunctional impact on the lungs.

"[105] It is found, that the naturally occurring cannabinoid compound delta-9-tetrahydrocannabinol (THC: C21H30O2), appearing in Cannabis, increase NO production in neonatal cardiac cells through the induction of the inducible nitric oxide synthase (iNOS) activity in a CB2 receptor dependent manner, while increasing endothelial nitric oxide synthase (eNOS) expression in diabetic hearts subject to ischaemia/reperfusion (I/R), thereby protecting cardiac cells from hypoxic damage, probably by pre-training the cardiomyocytes to hypoxic conditions, as an NOS inhibitor was able to block the THC-induced cardioprotective action.