Nitric Oxide

Nitric oxide is a very unusual molecule to be playing a role in physiological regulation. It is a free radical and volatile gas with a half-life in the body measured in seconds.

We have already briefly encountered nitric oxide in the context of oxygen radicals in phagolysosomes. There nitric oxide is synthesized to interact with the oxygen radicals in killing phagocytized microbes.

But curiously enough, nitric oxide also serves as a neurotransmitter in certain places. However, it is very different from other neurotransmitters in that is can easily diffuse over short distances and affects more than one cell.

Also, in blood vessels nitric oxide is released as a paracrine that relaxes smooth muscle cells. This leads to the dilation of blood vessels.

Nitric oxide synthesis begins when the enzyme nitric oxide synthase(NOS) is activated. This enzyme acts on an amino acid (L-arginine) to create nitric oxide.  There are three forms of nitric oxide synthase, which correspond to its three areas of action:  phagocytes, neurons, and endothelial cells of blood vessels.

When nitric oxide acts as a regulatory molecule, it diffuses to and activates a guanylyl cyclase that is located in the cytosol of the target cell (soluble guanylyl cyclase). Guanylyl cyclase converts GTP to cyclic GMP (cGMP), which then serves as the second messenger that causes the cellular action.

The diagram to the right shows how activation of nitric oxide synthase in an endothelial cell leads to dilation of a blood vessel. The stimulus, for example, might be a regulatory molecule that activates the nitric oxide synthase in the endothelium. The resulting nitric oxide diffuses to the surrounding smooth muscle cells, increasing cGMP which leads to relaxation of the smooth muscle around the the periphery of the blood vessels. This allows the blood vessel to dilate, allowing greater blood flow.

Several important drug actions revolve around nitric oxide. Nitroglycerin is converted to nitric oxide in the blood, which is why it dilates of blood vessels serving the heart.

Sildenafil (ViagraŽ) and similar drugs for treating erectile dysfunction specifically block a form of phosphodiestase found in the penis. The function of the phosphodiesterase is to break down cGMP. Sildenafil causes more cGMP to be present, and thus more dilation of the blood vessels supplying blood to the erectile tissue in the penis .

(Nitric oxide can also be breathed as a gas to dilate blood vessels in the lungs in certain respiratory disorders, although this is primarily an experimental use at present.)

Fill-in Answer Correct False Correct Answer
1. Fill in the blank.  Activation of ________ leads to increased nitric oxide.
2. What is the product formed by the enzyme guanylyl cyclase?
3. What is the effect of nitric oxide produced by endothelial cells, blood vessel dilation or constriction?
4. Does increased cGMP cause smooth muscle contraction or smooth muscle relaxation?
5. Do phosphodiesterase inhibitors such as sildenafil lead to more or less cGMP?

(Spelling must be correct)