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THE best way to honor the memory of Robert F. Furchgott, who died on
May 19 at the age of 92, is to retell the story of the biochemical
nitric oxide (NO) and his role in its elucidation.
NO was discovered in 1774 by the British
chemist, Joseph Priestley.
Pure NO is a poison; for a long time it was used
primarily to produce nitric acid for industry, nitrate fertilizer
for agriculture and nitrates or nitrites for households to preserve
meats.
NO is the simplest stable molecule with an odd
number of electrons. This accounts for its high chemical reactivity.
With oxygen it forms a gas called nitrogen oxide (NO2). Those of us
who had gone through a course in inorganic chemistry doubtless
remember that NO also reacts with metals.
Until recently NO was of little interest to
biochemists. To the lay public, NO was a pollutant that caused acid
rain and smog.
Things changed in the ’90s. In 1992, Science
named NO the molecule of the year, citing it as “a molecule of
versatility and importance that has burst on to the scene in many
guises. In the atmosphere it is a noxious chemical, but in the body
in small controlled doses it is extraordinarily beneficial.”
All this began in the late ’80s when this
light, gaseous, reactive molecule was found to have a part in body
functions.
Specifically, NO is important for digestion, for
the control of blood pressure and for protecting the body against
harmful microorganisms.
It’s also being investigated for possible use
in the treatment of heart disease, shock, cancer, pain and pulmonary
hypertension in premature babies.
How does it work?
In the body, it’s made from arginine, an amino
acid, by an enzyme, NO synthase. When released by the cells in the
walls of blood vessels, it relaxes muscle cells, causing the blood
vessel to dilate and blood pressure to fall.
For the body’s defense system, NO is an
anti-tumor agent. In cases of a stroke, NO triggers a
neurotransmitter in the brain to relay a warning signal. In the
digestive system, the peristaltic movement of the gut depends on NO.
Lack of it may cause pyloric stenosis in infants that’s
potentially fatal. There’s some evidence that NO in the brain
affects learning and memory.
The best known and most profitable outcome of
the current intensive research on NO is the conclusive finding that
in male mammals, NO converts sexual excitation into penis erection.
The brain causes NO to be released into the blood vessels of the
penis.
It’s estimated that 10 percent of all human
males suffer from impotency of varying degrees. The action of NO in
enlarging blood vessels was key to the development of the drug
sildenafil citrate by Pfizer better known by its brand name Viagra.
The discovery of Viagra was somewhat
serendipitous as Pfizer’s original goal was to develop a drug to
treat heart disease.
Robert Francis Furchgott was born on June 4,
1916 in Charleston, South Carolina, USA. He earned a degree in
chemistry from the University of North Carolina and a Ph.D. in
biochemistry from Northwestern University.
For many years after graduation he worked at the
State University of New York Downstate Medical Center in Brooklyn,
New York City, where he conducted ingenious experiments that proved
that NO causes blood vessels to widen and the adjacent smooth muscle
cells to relax.
In 1986, Dr. Furchgott announced to a conference
at Mayo Clinic in Rochester, Minnesota that he had identified the
molecule responsible for the “relaxing factor.” It was nitric
oxide.
He continued his research with Dr. Louis J.
Ignarro and Dr. Ferid Murad. For their discovery that NO transmitted
signal in the cardiovascular system, mediated blood pressure and
blood circulation, they were awarded the Nobel Prize for Physiology
in 1998.
opinion@manilatimes.net
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