Understanding Blood Flow

How can you give a man an erection with a pill? You can't give a man a pill loaded up with a general smooth-muscle relaxer like phentolamine -- that would cause all of the smooth muscle throughout the man's body to relax, and that might create a lot of problems. What you need is a drug that acts only on the smooth muscle in the arteries of the penis.

To understand how to make a penis-specific drug, think about the way blood flows in your body. Your body has just one pump -- the heart. But different parts of the body need different amounts of blood at different times.

For example:

• If you eat a big meal, your body needs to send more blood to the stomach and intestines to help with digestion.

• If you are running in a marathon, your body needs to send more blood to your arm and leg muscles, and it may want to cut most of the blood flowing to the stomach (and other nonessential organs) in order to save oxygen for the legs.

What your body needs, in other words, is a set of valves that it can use to increase and decrease blood flow to certain parts of the body. And your brain needs a way to control those valves so it can turn them on and off when necessary.

The penis is one of the places in the body where the brain needs to be able to turn the blood flow on and off with a valve. To understand how the brain controls this particular valve, let's start with the basic concept at work: How does the brain control blood flow to different parts of the body?

Turning Valves On and Off
In the human body, the "valves" open and close using muscles in the walls of arteries. When these muscles relax, the arteries open up and blood flow increases. The valves respond to chemical messages that the brain can control.

The mechanism that the body uses to "open a valve" in any part of the body involves four steps:

1. The brain sends a signal down a particular nerve fiber. This nerve fiber ends in an NANC nerve cell in an artery, somewhere near the point where blood flow needs to change. NANC stands for nonadrenergic-noncholinergic, and what it means is that the NANC nerve cell is able to create nitric oxide.

2. The NANC nerve endings inject nitric oxide into the blood and surrounding cells.

3. The nitric oxide stimulates an enzyme called guanylate cyclase in nearby cells, and this enzyme starts producing a chemical called cyclic guanosine monophosphate (cGMP).

4. cGMP tells smooth muscles that line an artery to relax. When they relax, blood flow increases.

This mechanism is a simple little chemical machine, and the brain uses it to increase blood flow in several different parts of the body. But there is one final part to this chemical machine: Another enzyme called phosphodiesterase (PDE) deactivates the cGMP.

The brain sends signals to NANC cells in the artery. The NANC cells release nitric oxide (NO). Nitric oxide acts as a signaling molecule and stimulates an enzyme called guanylate cyclase in nearby cells. The guanylate cyclase converts a chemical called GTP into another chemical called cGMP. cGMP causes muscles in the walls of the arteries to relax. This relaxation increases blood flow. Meanwhile, PDE is decomposing the cGMP and turning it back into GTP. There is a cycle -- guanylate cyclase turns GTP into cGMP, and PDE turns cGMP into GTP. Nitric oxide turns the cycle on.

­cGMP is produced as long as the brain is sending messages down the nerve fibers in the artery, which generate nitric oxide and keep the cycle going. When the brain stops sending the signal, all of the cGMP goes away because PDE is deactivating it. This way, the brain can turn valves on and off whenever it wants to.

So how does this relate to an erection?

When the brain gets aroused, it sends a signal to the penis. Nerve cells in the penis' corpora cavernosa start producing nitric oxide, which leads to the creation of cGMP. The cGMP causes arteries in the corpora cavernosa to dilate, causing lots of blood to flow into the penis. The extra blood flowing in causes the penis to inflate like a balloon. An erection occurs.

When a man suffers from erectile dysfunction, there can be many reasons for the problem. But one of the most common reasons, especially in older men, is that the arteries in the penis aren't dilating enough when the brain sends the signal. The man is aroused, and the nerves in the penis are producing NO; but the amount of cGMP produced is not enough to maintain an erection.

The way that Viagra goes about solving this problem is quite ingenious, and involves the following question: How can you create a drug that affects only the penile valve?