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Nitric oxide is a gas. It is highly reactive; that is, it participates in many chemical reactions. (It is one of the nitrogen oxides ("NOx") in automobile exhaust and plays a major role in the formation of photochemical smog [Link].)
But NO also has many physiological functions.
They share these features:
NO relaxes the smooth muscle in the walls of the arterioles. At each systole, the endothelial cells that line the blood vessels release a puff of NO. This diffuses into the underlying smooth muscle cells causing them to relax and thus permit the surge of blood to pass through easily. Mice whose genes for the NO synthase found in endothelial cells (eNOS) has been "knocked out" suffer from hypertension.
Nitroglycerine, which is often prescribed to reduce the pain of angina, does so by generating nitric oxide, which relaxes the walls of the coronary arteries and arterioles.
|Three of the pioneers in working out the biological roles of NO shared a Nobel Prize in 1998 for their discoveries. The award to one of them, Ferid Murad, honored his discovery that nitroglycerine works by releasing NO. This seems particularly appropriate because Alfred Nobel's fortune came from his invention of making dynamite from nitroglycerine!|
NO also inhibits the aggregation of platelets and thus keeps inappropriate clotting from interfering with blood flow.
Release of NO around the glomeruli of the kidneys increases blood flow through them thus increasing the rate of filtration and urine formation.
|Link to discussion of kidney function.|
The erection of the penis during sexual excitation is mediated by NO released from nerve endings close to the blood vessels of the penis. Relaxation of these vessels causes blood to pool in the blood sinuses producing an erection.Three popular prescription drugs
Recent evidence suggests that NO's job in reproduction is not finished with producing an erection. At the moment of contact, release of NO by the acrosome of the sperm activates the egg to complete meiosis II and the other steps of fertilization.
Nitroglycerine has helped some women who were at risk of giving birth prematurely to carry their baby to full term.
The NO produced by eNOS (NOS-3) inhibits inflammation in blood vessels. It does this by blocking the exocytosis of mediators of inflammation from the endothelial cells.
NO may also block exocytosis in other types of cells such as macrophages and cytotoxic T lymphocytes (CTL).
NO affects secretion from several endocrine glands.
For examples, it stimulates
Hemoglobin transports NO at the same time it carries oxygen [Link to discussion]. When it unloads oxygen in the tissues, it also unloads NO.
In severe deoxygenation, NO-sensitive cells in the medulla oblongata respond to this release by increasing the rate and depth of breathing.
In laboratory animals (mice and rats), NO is released by neurons in the CA1 region of the hippocampus and stimulates the NMDA receptors there that are responsible for long-term potentiation (LTP) — a type of memory (and learning).
The ease with which NO diffuses away from the synapse where it is generated enables it to affect nearby synapses. So what may have begun as a localized action becomes magnified.
Laboratory rats treated with inhibitors of NOS synthesis fail to develop and/or retain learned responses such as the conditioned response.
Mice whose genes for nNOS have been knocked out are healthy but display abnormal behavior, e.g., they kill other males and try to mate with nonreceptive females.
NO aids in the killing of engulfed pathogens (e.g., bacteria) within the lysosomes of macrophages.
Mice whose genes for the NO synthase found in macrophages (iNOS) have been knocked out are more susceptible to infections by intracellular bacteria like Listeria monocytogenes.
Th1 cells, the ones responsible for an inflammatory response against invaders, secrete NO.
Harmless bacteria, living as commensals at the rear of our throat, convert nitrates in our food into nitrites. When these reach the stomach, the acidic gastric juice (pH ~1.4) generates NO from them. This NO kills almost all the bacteria that have been swallowed in our food.
(Since the dawn of recorded human history, nitrites have been used to preserve meat from bacterial spoilage.)
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|Link to a discussion.|