Nitric oxide Functions

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 is synthesized within cells by an enzyme NO synthase (NOS).

The human (and mouse) genome contains 3 different genes encoding NO synthases.

nNOS (or NOS-1): found in neurons (hence the "n").

eNOS (or NOS-3): found in the endothelial (hence the "e") cells that line the lumen of blood vessels.

iNOS (or NOS-2): found in macrophages. (the "i" stands for "inducible"). Whereas the levels of nNOS and eNOS are relatively steady, expression of iNOS genes awaits an appropriate stimulus (e.g., invasion by a pathogen).

NO diffuses freely across cell membranes.

There are so many other molecules with which it can interact, that it is quickly consumed close to where it is synthesized.

Thus NO acts in a paracrine or even autocrine fashion — affecting only cells near its point of synthesis.

This page examines some of the functions of NO.

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 has been "knocked out" suffer from hypertension.

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!

Release of NO around the glomeruli of the kidneys increases blood flow through them thus increasing the rate of filtration and urine formation.

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

sildenafil (Viagra®)

vardenafil (Levitra®)

tadalafil (Cialis®)

enhance this effect by the mechanism described .

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.

The wavelike motions of the gastrointestinal tract are aided by the relaxing effect of NO on the smooth muscle in its walls. NO also inhibits the contractility of the smooth muscle wall of the uterus. As the moment of birth approaches, the production of NO decreases.

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

Some motor neurons of the parasympathetic branch of the autonomic nervous system release NO as their neurotransmitter. The actions of NO on penile erection and peristalsis are probably mediated by these nerves.

In severe deoxygenation, NO-sensitive cells in the medulla oblongata respond to this release by increasing the rate and depth of breathing.