As you can see in the diagram below, the penis is made up of three chambers, the bottom one of which, the corpus spongiosum, surrounds the urethra, the passage through which semen and urine exit the body. Above and to each side of the urethra are the two corpora cavernosa (singular corpus cavernosum). Each of these chambers is made up of many small sinusoids, or tissues spaces into which the blood can flow; the sinusoids are surrounded by smooth muscle tissue which controls the flow of blood into and out of the sinusoids as it contracts and relaxes.

As you would expect there is a network of arteries and veins which supply blood to, and remove it from, the sinusoids: the larger arteries and veins in this network are known as the sinusoidal arteries and the emissary veins respectively. Surrounding the corpora cavernosa is a fibrous layer of tissue called the tunica albuginea. The emissary veins are located between the corpora cavernosa and their respective tunica albuginea.

A word about smooth muscles

There are several types of muscles in the human body: smooth muscle, such as that found in the penis, is a type which is not under voluntary or conscious control. Thus you cannot control the muscles inside the  internal chambers of the penis in the way, for example, that you can control the movement of your arm. Furthermore, these smooth muscles are innervated with different nerve cells to those of the voluntary muscular system. 

Function

When the penis is flaccid, the smooth muscles which surround the arteries supplying the corpora cavernosa with blood are contracted; this constricts the arterial network, which therefore is unable to pass blood into the corpora cavernosa. The muscles do not close the vessels completely, however, for this would starve the penis of blood; rather, they constrict the vessels just enough that the penis remains flaccid. The cavernous smooth muscle is also contracted with the same effect. By contrast, the penile veins and venules (smaller veins) are unaffected, and blood flows out of the penis quite easily.

Under the influence of sexual stimulation, the smooth muscles of the penile arteries and corpora cavernosa relax. This allows an increased amount of blood to flow into the sinusoidal spaces, which begin to swell and press up against the surrounding tunica albuginea. As the tissues swell, the venules and veins of the corpora cavernosa are compressed so that their internal diameter is reduced and their ability to transport blood away from the corpora cavernosa is significantly reduced. At the same time, the major veins of the penis, the emissary veins, are squeezed between the tunica and the walls of the corpora cavernosa, so they too can  transmit less blood away from the penis. Since the blood is trapped in the penis, it gradually becomes engorged ands stiff, in a state of erection, in fat. At full erection, the blood pressure in the corpora cavernosa is the same as the pressure of blood leaving the heart. 

The loss of erection is exactly the same process in reverse: the smooth muscles contract and the arteries again become constricted. This reduces the inflow of blood into the penis. At the same time the smooth muscles of the sinusoids become constricted which reduces the external pressure on the venules and the emissary veins and allows the blood to flow out. 

Erectile Dysfunction (ED) and its treatment

Estimates suggest up to 10% of the male population suffers from erectile dysfunction. As men get older, the possibility of ED becomes greater. In some males ED takes the form of a total inability to achieve an erection. In others the erection may be incomplete or last insufficiently long to achieve any or satisfactory sexual intercourse. 

In the early 1990's, the most widely used treatment for erectile dysfunction was self-injection, directly into the corpora cavernosa, of various drugs. This injection had to be done shortly before sexual intercourse was expected to take place. The drug most often used was called papaverine, which relaxes the smooth muscles of the penis. But it was an inconvenient and uncomfortable treatment which found limited acceptance among men, not least because such injections can cause scarring and damage to the lining of the corpora cavernosa.

As an alternative to these injections, some men were taught to introduce drugs directly into the urethra: this could produce side-effects including a burning sensation. Other approaches which were tried around this time included the use of suction devices and prostheses, the use of glyceryl trinitrate patches applied to the penis, and, most desperately of all, surgery to try and increase arterial blood  supply to the penis. 

How smooth muscles work

In the type of smooth muscle in the penis, each cell relaxes when it receives a small dose of a "chemical messenger" called nitric oxide or NO for short. Nitric oxide is produced or released from at least two sources: the endothelium cells found around the smooth muscles and  the nerves which service smooth muscle.

In both cases the nitric oxide is produced by a reaction from a chemical called L-arginine. The chemical reaction is catalyzed by an enzyme called nitric oxide synthase. The nitric oxide produced by these two methods enters the smooth muscle cells and activates another enzyme (called guanylate cyclase) which converts another chemical called guanosine triphosphate (GTP) to cyclic guanosine monophosphate (cGMP). 

cGMP in turn activates certain other intracellular enzymes (called protein kinases) which cause or promote chemical reactions which relax the smooth muscle. cGMP can itself be inactivated. A group of enzymes, called phosphodiesterases or (PDEs), cause cGMP to be turned into a chemical which is ineffective to relax muscle. This ineffective chemical is known as 5-GMP. Thus turning cGMP into 5-GMP has the effect of removing the agent which causes the muscle to relax. 

There are actually other, similar, reactions in the tissues of the penis, but they follow the same principle as the reaction pathway outlined above: and the crucial thing is that each pathway is inhibited by the action of a PDE enzyme (of which there are five types, each controlling a different sequence of chemical events in the tissues of the penis). Obviously, since PDE enzymes inactivate the compounds like cGMP which promote relaxation of the smooth muscles, then any chemical which inhibits the action of the PDE enzymes will leave more cGMP to relax the smooth muscles and therefore should be offer a way of promoting the erectile capacity of the penis.

To sum up, from the journal Science, Dec 1992:

"This year [1992], scientists proved definitively that in males, NO translates sexual excitement into potency by causing erections. Key pelvic nerves get a message from the brain and make nitric oxide in response. NO dilates blood vessels throughout the crucial areas of the penis, blood rushes in, and the penis rises to the occasion."  

NO and Viagra

Viagra is a potent inhibitor of cyclic guanosine 3- 5-monophosphate phosphodiesterases (cGMP PDEs). It blocks the ability of the phosphodiesterase enzyme (PDE) to turn cGMP into 5-GMP. The result is that cGMP levels remain high and it is this high level of cGMP which is responsible for maintence of the erection in the penis.