Scientists looking for the causes of impotence and ways to cure it are zeroing in on nitric oxide, an invisible gas that is proving to play surprising and crucial roles in a growing list of biological processes.
Researchers at the Johns Hopkins School of Medicine say they have found evidence that nitric oxide is manufactured by the nerve cells that trigger erections in male rats, and appears to be the key neural "switch" that gets the erection started.
They say the discovery may open the door to new treatments for millions of impotent men, and for a smaller group who suffer from priapism -- painful, persistent erections unrelated to sexual arousal. Priapism is experienced by 40 percent of all men with sickle cell anemia.
"Now that we understand the system better, we may be able to provide better interventions when it goes awry," said Dr. Arthur L. Burnette, a resident urologist at Hopkins who led the study.
A drug, salve or patch to relieve some forms of impotence or priapism may still be several years away, he said. But, "we have clearly shown the nitric oxide is important in a physiological way for erection, and that it is derived from the nerve."
Further research already under way is aimed at identifying nitric oxide production in nerves serving the human penis, and comparing nitric oxide production in groups of normal and impotent men, he said.
The research at Hopkins is described in today's issue of Science, the journal of the American Association for the Advancement of Science. Co-authors include Hopkins cardiologist Dr. Charles Lowenstein, neuroscience director Dr. Solomon Snyder, Ph.D- and M.D.-candidate David Bredt and urologist Dr. Thomas S. K. Chang.
The nitric oxide molecule is composed of one nitrogen atom and one oxygen atom. It is a highly reactive gas that lasts only about five seconds before combining with something else. Pumped into the atmosphere as a byproduct of combustion, it combines with water to form acid rain, which is damaging to trees and to life in ponds and streams.
"You would never think that anything as noxious as that would have any role in biology at all," said Dr. Snyder. But in the last six years, he said, scientists have begun to recognize that nitric oxide produced by the body in minute amounts is "one of the most important messenger molecules in all biology."
Studies have identified nitric oxide as the "bullet" manufactured by disease-fighting cells of the immune system to kill foreign organisms. It has also been found to play a role in the transmission of nerve impulses in brain cells, the intestines, the lungs, pituitary gland and other organs throughout the body.
Dr. Lowenstein said researchers also found that the release of nitric oxide by nerves in the blood vessels causes them to relax, lowering blood pressure. Drugs that promote or block nitric oxide production may one day become a preferred way to regulate blood pressure, he said.
The latter discovery sent several groups of scientists looking for nitric oxide's role in male potency, since erections are initiated by nerve signals that relax the blood vessels in the penis. The expanded vessels allow more blood to flow into the penis than flows out, producing the erection.
Dr. Snyder said impotence is experienced by as many as one man in 10. Once thought to be largely psychological in origin, 80 percent to 90 percent of all cases of impotence are now thought to be due to physical abnormalities.
Arteriosclerosis -- the thickening and hardening of artery walls, restricting blood flow -- is one common cause. Nerve damage due to diabetes is another.
Priapism is less common, but does affect 40 percent of men with sickle cell anemia, a blood disorder that afflicts 1 in 400 blacks born in the United States.
It's not clear yet how many cases of impotence or priapism might be due to abnormalities in the production of nitric oxide.
Scientists at the University of California at Los Angeles reported in January that they had identified nitric oxide as a key factor in initiating erections.
Dr. Burnette and his team at Hopkins took the work further by identifying the nerve cells serving penile blood vessels in rats as the source of the gas. Their experiments also showed that drugs which block nitric oxide production in those nerve cells also ended electrically stimulated erections.
If the same mechanism is proved to exist in humans, it may be possible to get an erection started by applying drugs that release nitric oxide directly into the penis, Dr. Burnette said.
One candidate is nitroglycerin -- commonly used by angina patients to relax blood vessels serving the heart. To treat impotence, doctors might offer patients a nitroglycerin ointment, salve or slow-release patch -- more appealing alternatives to currently available mechanical implants, or drugs injected directly into the penis.