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Nitric Oxide in Biology and Medicine
Less than two months before his death in December 1896,
Alfred Nobel wrote a note to a colleague: "Isn't it the irony of fate that I
have been prescribed nitro-glycerin, to be taken internally! They call it
Trinitron, so as not to scare the chemist and the public." Nobel suffered
recurring attacks of the intense chest pain known as angina pectoris, and
physicians of his day knew that nitroglycerin--the active ingredient in
dynamite--provided effective relief. The irony, of course, was that the Swedish
inventor and industrialist had made much of his considerable fortune from
developing and manufacturing dynamite. Moreover, from his own laboratory
experiments, Nobel had learned that exposure to the chemical caused severe
headaches. He declined to take it for his angina.
Although nineteenth-century scientists understood why nitroglycerin was a
potent explosive, they had no idea what made it an effective treatment for
angina. Somehow it relaxed the smooth muscles that surround blood vessels,
allowing the vessels to dilate so that more blood could flow to the starved
heart muscle. The secret of nitroglycerin emerged at last in the 1970s, when
researchers realized that it works by reacting in the body to form a messenger
molecule called nitric oxide, or NO.
Outside the body, NO is an unstable, potentially toxic gas that forms in
lightning strikes and car exhaust. But as a messenger molecule inside the body
it plays a crucial regulatory role. Every cell type and tissue sends and
receives messages--telling muscle cells when to contract, for instance, or fat
cells when to release their stores. Several message systems regulate our web of
blood vessels so that they deliver oxygen-carrying blood to the tissues and
organs that need it most while also keeping our blood pressure at an
appropriate level. The various messengers selectively dilate or constrict blood
vessels, diverting blood flow, as the body requires--to the gastrointestinal
tract after a meal, for example, or to the muscles of movement in an emergency.
Nitric oxide is at the center of the most important relaxation system, thus
explaining why nitroglycerin helps angina patients. But NOW's importance does
not stop with angina. Inhaled NO can help premature babies when the blood
vessels in their lungs are not absorbing oxygen adequately. Local application
of NO-related drugs may prevent cells from growing and blocking repaired
arteries. Drugs that release NO at the site of an infection also may help
immune cells kill invading pathogens and tumor cells.
"From Explosives to the Gas That Heals" was written by science writer William
Wells, Ph.D., with the assistance of Drs. David Bredt, Robert Furchgott, Louis
Ignarro, Michael Marletta, Ferid Murad, Solomon Snyder, Steven Tannenbaum, and
Sir John Vane for Beyond DiscoveryTM: The Path from Research to Human Benefit,
a project of the National Academy of Sciences.
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