Nitric Oxide in the Body: Benefits and Dangers
A Simple and Important Molecule
Nitric oxide is a simple little molecule with big effects inside our body. Many biological molecules have a complex structure, but nitric oxide contains just two atoms—a nitrogen atom and an oxygen atom—and has the formula NO. It's sometimes called nitrogen monoxide.
NO has many important biological functions. It relaxes the walls of blood vessels, causing vasodilation (widening of the vessels). This allows more blood to flow into the heart and other organs. It also acts as a signaling molecule between nerve cells. In addition, it plays an important role in our immune system and helps it to fight infections.
Research suggests that nitric oxide may have an effect on aging and longevity. The possession of intestinal bacteria that make NO enables Caenorhabditis elegans to live for significantly longer than members of its species without the bacteria. C. elegans (the abbreviated scientific name) is a roundworm and a popular organism in anti-aging studies. What applies to a roundworm may not apply to us, but it is known that the level of nitric oxide in our body decreases as we age. The idea that bacteria producing nitric oxide could be added to our intestine in order to help us live longer is a tantalizing thought.
Nitric oxide shouldn't be confused with nitrous oxide, which is commonly known as laughing gas. A nitrous oxide molecule contains two nitrogen atoms and one oxygen one. It acts as an anesthetic and is not a normal component of our body.
Nitric Oxide and the Heart
Role of NO in the Circulatory System
Nitric oxide in blood plays a vital role in keeping our circulatory system healthy. It causes vessels to widen and open up, allowing large quantities of blood to be transported. Blood without nitric oxide doesn't cause vessels to expand. This means that the blood can't flow as easily through the vessels.
Researchers have noticed that the longer that blood is stored before a blood transfusion, the more dangerous it is for the recipient. This seems to be due to the biochemical changes that take place as the blood ages, including loss of nitric oxide gas. Without NO, the donated blood may block the circulatory system because it can't move through the vessels properly. One scientist has shown that in lab animals adding nitric oxide to blood before a transfusion prevents blockage and allows the blood to flow freely.
Nitric oxide also lowers blood pressure. We have some control over this action via the food that we eat. A diet high in leafy green vegetables and beets (or beetroot) is known to lower high blood pressure. These vegetables are a good source of nitrates. Inside the body, the nitrates are converted to nitrites. The nitrites are then converted to nitric oxide. The nitric oxide expands blood vessels, which lowers blood pressure. The body also makes nitric oxide from an amino acid called L-arginine.
Blood Transfusions and Nitric Oxide Depletion
Three researchers—Robert F. Furchgott, Louis J. Ignarro, and Ferid Murad—discovered that NO acts as a signaling molecule in the circulatory system. In 1998 these scientists won the Nobel Prize for Medicine for their work with nitric oxide.
Nitroglycerin, NO, and Angina
In 1977, a researcher discovered that nitroglycerin causes the production of nitric oxide in the body. Nitroglycerin (or nitroglycerine) is one medicine given to people suffering from angina. During an angina attack, a person experiences chest pain due to a lack of oxygen in the heart, usually due to the narrowing of a coronary artery. Nitroglycerin expands the artery. The nitric oxide made from the nitroglycerin is responsible for the vasodilation.
Nerve cells, or neurons, communicate with each other by means of chemicals. These chemicals are known as neurotransmitters. A neurotransmitter is produced in advance and stored in small sacs called synaptic vesicles, which are located at the end of a neuron.
The region where one neuron ends and another begins is called a synapse. When a nerve impulse arrives at a synapse, the neurotransmitter is released from the first neuron into the tiny gap that is present between neurons. The neurotransmitter travels through the gap and attaches to receptors on the membrane of the second neuron. Once this union takes place, the second neuron is stimulated (or in some cases inhibited). Stimulation generates a nerve impulse. After it has done its job, the neurotransmitter is broken down or reabsorbed into a nerve cell.
Nitric oxide is a neurotransmitter, but it behaves differently from other neurotransmitters. It isn't produced in advance or stored but is made when it's needed. It does travel across the gap between neurons, but it travels into the second neuron instead of attaching to receptors and staying at the neuron's surface. It may also enter more than one neuron.
Nitric oxide isn't very stable and only exists for a short time. It's sometimes called a "gasotransmitter"—a gas that is made in the body and acts as a signaling molecule.
Functions in the Nervous System
Nitric oxide has many functions in the central nervous system (the brain and the spinal cord). It plays a role in:
- learning and memory
- controlling body temperature
- regulating food intake
- controlling the sleep-wake cycle
- regulating hormone release
- protecting nerves
The peripheral nervous system is made of nerves that leave the central nervous system and travel to the rest of the body. In the peripheral nervous system nitric oxide does the following:
- relaxes the muscles in the lining of the gastrointestinal tract
- relaxes the muscles in the lining of the urinary and reproductive tracts
Neuroprotection and Neurotoxicity
Although nitric oxide is very important in the nervous system, it's present in tiny quantities in our body. These quantities are neuroprotective— they protect the nerves from damage. Large amounts of nitric oxide kill nerve cells and are said to be neurotoxic, however. This might explain why the results of some research studies involving nitric oxide disagree with the results of other studies. For example, some research suggests that NO administered to a patient after a stroke helps the patient, while other research suggests that excess NO produced during strokes damages brain cells.
What Role Does Nitric Oxide Play in the Immune System?
Nitric oxide is made by macrophages, which are a type of white blood cell in our immune system. The NO kills bacteria and inhibits the replication of viruses.
Nitric oxide action is part of our innate immune response. This is a rapid, general, and non-specific response which is the same for any pathogen (organism that causes disease). Our other type of immunity is the acquired immune response, which involves an attack that is specific for each pathogen.
Nitric oxide is a controversial chemical with respect to cancer. Some evidence suggests that it helps the immune system fight cancer, while other evidence suggests that it can actually cause cancer.
C. elegans Swimming and Clumping
Aging and Longevity
Caenorhabditis elegans is a transparent roundworm that lives in soil. Like humans, the roundworm has bacteria that live in its intestine and produce substances that provide health benefits.
C. elegans feeds on a bacterium called Bacillus subtilis. Some of the bacterial cells survive and live in the animal's intestine, where they produce nitric oxide. The worms also eat Escherichia coli, another bacterium that lives in their intestine. Escherichia coli can't make nitric oxide, however.
Worms fed Bacilus subtilis live for about 50 percent longer than worms fed Escherichia coli. This is believed to be at least partly due to the presence or absence of nitric oxide.
One research experiment discovered that C. elegans worms fed normal B. subtilis lived for 15 percent longer than those fed a mutant form of the bacterium that lacked the gene for nitric oxide production. The experiment also confirmed a previous discovery that C. elegans can't produce nitric oxide itself.
Nitric Oxide Use in the Future
In the future, nitric oxide may be very useful as a medicine. A major problem will be ensuring that the concentration of the nitric oxide is high enough to be helpful but low enough to be safe, however.
In addition, researchers need to learn more about nitric oxide's effects on the body before it's used medicinally. It's a simple molecule but is involved in complex reactions. If NO is administered to treat one health problem, it's important that it doesn't cause another one.
The Vital Role of Nitric oxide from Oakland University
Nobel Prize in Medicine for Nitric Oxide Discovery from Circulation (an American Heart Association journal)
NYU Langone Medical Center. (2013, February 14). Nitric oxide: A little molecule's remarkable feat -- prolonging life, worm study shows. ScienceDaily. Retrieved August 1, 2017 from www.sciencedaily.com/releases/2013/02/130214132623.htm
Questions & Answers
How much L-arginine should be ingested each day?
L-arginine is an amino acid that is present in our diet. It’s found in meat, fish, dairy products, and beans. Most people obtain enough L-arginine as long as they eat a nutritious diet, so they don’t need to be concerned about the intake of the nutrient. A health care professional or a dietitian can recommend dietary methods to increase arginine intake if a person suspects that they aren’t eating enough.
L-arginine is converted to nitric oxide in the body, but it’s unclear whether ingesting the substance as a supplement will boost the nitric oxide level in everyone. Most people don’t need to take supplemental arginine, but people with certain medical problems might benefit from the substance. It’s important that a person consults a doctor before taking an arginine supplement, however. In a supplemental form, the substance can cause major side effects and interact harmfully with certain medications.
If a doctor thinks that supplement arginine will be useful for a patient’s specific medical problem and that the possible side effects of the supplement won’t be harmful to that patient, they’ll recommend a safe and potentially beneficial dose.
© 2013 Linda Crampton