Medical Nobel prize says yes to NO.

In the 1860s, Alfred Nobel invented dynamite, an explosive using the volatile compound nitroglycerin. Yet, when a doctor prescribed nitroglycerin to treat his heart disease, Nobel refused the treatment, believing it unlikely to work. Ironically, research that has helped explain how nitroglycerin can ease chest pains has now earned one of the famous prizes established by Nobel's riches.

Robert E Furchgott of the State University of New York Health Science Center in Brooklyn, Fetid Murad of the University of Texas Medical School in Houston, and Louis J. Ignarro of the University of California School of Medicine in Los Angeles share the 1998 Nobel Prize in Physiology or Medicine for "discoveries concerning nitric oxide as a signalling molecule in the cardiovascular system," the Karolinska Institute in Stockholm announced this week.

In 1977, Murad found that nitroglycerin and related drugs induce nitric oxide (NO) formation and that this gas relaxes the muscle cells that narrow and dilate blood vessels. Around 1980, Furchgott found that endothelial cells, which line the interior of blood vessels, produce a signaling molecule that causes nearby muscle cells to relax, thus regulating blood pressure.

Scientists didn't initially connect the two discoveries. Like other so-called free radicals, the highly reactive nitric oxide, a common air pollutant, was largely thought a destructive molecule not normally employed by the body. But as Furchgott and Ignarro, working independently, analyzed the nature of the endothelium's relaxing factor, the gas became a prime candidate. At a conference in 1986, each laid out a compelling case that nitric oxide was indeed the factor.

"This was bold, to say the least, because there was no reason to suspect that there was machinery for making nitric oxide" in the human body, notes Jack R. Lancaster Jr. of the Louisiana State University Medical Center in New Orleans, an editor of the journal NITRIC OXIDE.

Research into nitric oxide has blossomed since. Scientists have found the enzymes with which cells make the short-lived gas and have shown that it plays a role in activities as diverse as memory formation, tumor suppression, and immunity. Some brain cells communicate using the gas, and immune cells let loose bursts of nitric oxide to kill infectious organisms or cancer cells. By increasing blood flow, nitric oxide even plays a role in penile erections; the celebrated drug Viagra amplifies the actions of the gas. Physicians are also exploiting the effects of nitric oxide in several other ways. They administer it to premature infants to stimulate blood flow to underdeveloped lungs, for example.

"The NO field has outgrown its original discovery," says Jonathan S. Stamler of the Duke University Medical Center in Durham, N.C., who studies nitric oxide's interactions with hemoglobin (SN: 3/23/96, p. 180). "The impact has been truly remarkable. The ramifications apply to every organ system and cellular response. You name it... and nitric oxide has been implicated."

Considering that too much nitric oxide can damage cells, "it's astounding nature chose it to perform so many functions," adds Lancaster.