Nitric Oxide

Nitric oxide is a colourless free-radical gas. A biological agent in the 1980s, it has evolved to play a key vasodilating role in heart and nervous system signalling.

What is nitric oxide?

Discovery

In 1998, three researchers were awarded the Nobel Prize for their work in the identification of nitric oxide. They showed that this molecule is able to make vascular smooth muscle cells relax, resulting in vasodilation.

Of the Nobel Prize winners, one researcher was a pharmacologist in New York who was working on the identification of a molecule that caused smooth muscles in blood vessels to relax. He termed this molecule EDRF—endothelium-derived relaxing factor.

In 1977, a second researcher in Virginia showed that nitroglycerin releases nitric oxide as a signalling molecule to dilate the blood vessels.

In 1986, the third winner, a pharmacology professor in California, discovered that EDRF is identical to nitric oxide. This discovery led to many more research endeavours into the potential of nitric oxide in the human body.

Functions

With the interest generated by nitric oxide, many important functions of the molecule have been identified. These include its role in the regulation of blood pressure, the functioning of the immune system, and activities of the central nervous system, including memory and behaviour.

Although the potential for the use of nitric oxide in healing disease states continues to be researched, it is now available as an approved supplement. Studies on its uses have focused primarily on the treatment of hypotension or hypertension, Alzheimer’s disease, and sepsis.

Role in the body

Nitric oxide is made when L-arginine is combined with oxygen. An enzyme called nitric oxide synthase converts those substances to nitric oxide and citrulline.

Nitric oxide has a role in body systems such as the immune system, nervous system, and cardiovascular system. In the immune system, macrophages produce high levels of nitric oxide in the killing of tumour cells and bacteria. Nitric oxide is beneficial to the nervous system in that it acts as a neurotransmitter to regulate programmed cell death of neurons. In the cardiovascular system, nitric oxide is released as the heart pumps blood to allow the smooth passage of blood within the blood vessels.

Nitric oxide may also inhibit metastasis—the spreading of a tumour or cancer to other parts of the body—by preventing tumour cells from sticking to inner blood vessel walls.

Heart health

Nitric oxide appears to have a role in cardiovascular health during normal physiological processes as well as in disease states. Blood vessels are lined with a single layer of cells that maintain chemical balance. Nitric oxide is one of the molecules involved in vasodilation, and low levels have been shown to be a risk factor for cardiovascular events.

Nitric oxide prevents the cells of the blood vessels from multiplying, prevents platelets from aggregating, and prevents other inflammatory cells from building up in the vessels. If there is excess oxidative stress in the blood vessels, nitric oxide activity becomes impaired and asymmetric dimethylarginine (ADMA) accumulates and further inhibits nitric oxide production. Heart disease research is attempting to determine ways to maximize nitric oxide enzymes to allow increased nitric oxide production within vessel walls.

Improve your level of nitric oxide

Meditation has been studied for its effect on raising nitric oxide levels through the relaxation response. In a small meditation study, the authors were able to show a relationship between a deeper relaxation response and a higher nitric oxide level. The nitric oxide level was measured after meditation and shows promise for using meditation in stress-related conditions.

Research is also being conducted on the use of cocoa flavanols to optimize nitric oxide levels through biochemical pathways. One interesting initiative tracked the consistently low blood pressure of Kuna Indians of Panama. Their diet is rich in cocoa products when they live with their tribe.

When tribe members moved to urban areas of Panama, however, their blood pressure was noted to increase, and there was a sharp decline in the amount of cocoa consumed. The researchers concluded that flavanol-rich foods (from cocoa) were associated with lower blood pressure in their study groups.

Diets high in fruits and vegetables provide more dietary polyphenols. These polyphenols are being studied in terms of increased consumption and consequential lower blood pressure. The research is focused on findings that polyphenols regulate nitric oxide bioavailability and thus regulate blood pressure.

L-arginine and heart health

L-arginine is a semi-essential amino acid, which means the body can produce it, but at times supplementation is required. Arginine can be sourced from the diet in the form of tree nuts, red meat, poultry, dairy, or fish. It is converted in the body to nitric oxide by the enzyme nitric oxide synthase.

L-arginine is used to support heart health, as it dilates blood vessels and allows for less-compromised blood flow. Conditions for which L-arginine is used include congestive heart failure, high blood pressure, coronary artery disease, erectile dysfunction, and chest pain.

Doses of 3 to 8 g per day appear to be safe, and a typical Western diet provides 5 g per day. It is important to discuss the use of L-arginine with your health care practitioner. There may be contraindications to its use with pre-eclampsia (high blood pressure during pregnancy) and with certain heart patients.