Stockholm, SWEDEN (10/12/98)- Three American researchers
will receive this year's Nobel Prize in Physiology or Medicine for their
work on nitric oxide and the heart.
The three researchers are Professor Robert
F Furchgott, Department of Pharmacology, State University of New
York; Professor Louis
J Ignarro Department of Molecular and Medical Pharmacology,
UCLA School of Medicine; and Professor Ferid
Murad Department of Integrative Biology, Pharmacology and Physiology,
University of Texas Medical School at Houston.
"The
discovery of nitric oxide and its function is one of the most important
in the history of cardiovascular medicine," says Valentin Fuster, M.D.,
Ph.D., president of the American Heart Association. "It has allowed
us to improve certain treatments of patients and has given us the basis
to explore other mechanisms in the body which may contribute to cardiovascular
disease."
Graphic: The arteries
are sites of a very common disease, atherosclerosis. Here, an artherosclerotic
plaque has formed in a coronary artery. It consists of cholesterol, inflammatory
cells, and fibrosis, and it reduces the space for blood flow in the artery.
Click for more graphics.
The prize-winning researchers helped elucidate the key role nitric oxide
plays as a signalling molecule in the cardiovascular system. Their work
showed that NO is not like other signalling molecules. Their discovery
that NO gas that is produced by one cell, penetrates through membranes
and regulates the function of another cell revealed a new principle for
signalling in biological systems. NO differs from other neurotransmitters
and hormones in that it is not regulated by storage, release or targeted
degradation, but rather solely by synthesis.This discovery is all the more
amazing considering that NO, a compound more often associated with air
pollution, is very unstable, and is converted to nitrate and nitrite within
10 seconds of its creation.
Nitric oxide is involved in numerous physiological processes. A lack
of nitric oxide in the bloodstream, or a lack of reactivity by the blood
vessels to nitric oxide, can narrow the vessel opening, thus raising the
blood pressure. When NO is produced by the innermost cell layer of the
arteries, the endothelium, it rapidly spreads through the cell membranes
to the underlying muscle cells. Their contraction is turned off by NO,
resulting in a widening of the arteries. NO has also recently been shown
to play a key role in prevention of clot formation in the major vessels
of the heart.
Nitroglycerine has been prescribed for patients with heart disease since
the time of Alfred Nobel, founder of the Nobel Foundation. Alfred Nobel's
famous invention, dynamite, is a less explosive form of nitrooglycerine.
While it has been used for 100 years to treat chest pain assocaited with
heart disease, it was only recently discovered that nitroglycerine
acts by releasing NO gas. New, more selective drugs based on this knowledge
are in development.
It is hard to find a physiologic process in which NO does not play some
role. When activated in nerve cells, NO can modulate many functions,
from behaviour to gastrointestinal motility. NO is important for the olfactory
sense and the capacity to recognise different scents. In the immune system,
NO is produced in white blood cells, making them toxic to invading bacteria
and parasites. There are also indications that NO may help prevent or slow
tumor development. Recent treatments for impotence capitalize on the role
of NO in initiating erection.
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