At the end of the 20th century, a scientist willing to imagine a molecule that would control blood pressure, erection and the opening of body orifices, capable of fighting bacteria, parasites and tumors, and acting as a messenger between neurons involved in learning, memory, sleep or pain, he would have earned the nickname “crazy professor”.
If, furthermore, this crazy genius blamed all these actions on a toxic gas with a ridiculously simple structure (one atom of oxygen and one of nitrogen, the two most common elements in the atmosphere), his colleagues would not have even bothered in refuting it.
However, this magical molecule exists and, thanks to its study, today the lives of hundreds of children with congenital respiratory problems are saved and helpless patients are helped to generate new lives. The story of nitric oxide (NO) illustrates how loose scientific dogma is and how sometimes unrelated discoveries converge into a brilliant idea that improves our lives.
an amazing discovery
In 1987, the journal Nature reported the discovery of the physiological action of NO as an arterial vasodilator . A surprising and controversial finding, since it is an inorganic, gaseous and extremely reactive molecule, characteristics that make it unique among molecular messengers.
Until then, NO had little interest for scientists, who were only concerned with its activity as an environmental pollutant: it forms part of the toxic fumes from car exhaust and, released into the atmosphere, contributes to the formation of acid rain. For this reason, the Guatemalan scientist Salvador Moncada , protagonist of the discovery, adapted an instrument used in the control of emanations from exhaust pipes in his first experiments to measure the biological concentrations of the gas.
Five years later, Science magazine proclaimed NO molecule of the year and Salvador Moncada established himself as one of the most cited scientists of all time.
From that moment on, research on nitric oxide did not stop growing: its role in the cardiovascular system was soon joined by other actions in the central nervous and immune systems. The success of Viagra, a drug that potentiates the effects of NO, captured the public’s attention .
a turbulent history
The history of this ugly duckling of chemistry goes back many years to his “wonderful decade”. In the mid-19th century, the beneficial effects of amylonitrile in the treatment of angina pectoris were discovered. The new drug soon became the crown jewel of Victorian medicine, as reflected in Arthur Conan Doyle’s Sherlock Holmes story “The Case of the Resident Patient .” Without knowing it, the doctors administered a molecule that breaks down in the body, releasing NO.
It took more than a century for the effect of amylonitrile to be associated with the physiological action of NO. However, this gas was not unknown to nineteenth-century chemists. Its toxicity had been dramatically proven in 1829 by Humphrey Davy , father of electrochemistry and discoverer of the anesthetic properties of another nitrogen oxide, NO 2 or laughing gas. He died as a result of inhaling it.
Years later, during the First World War, doctors assigned to explosives factories noticed in their routine controls that the workers who handled nitroglycerin, another NO-releasing compound, had abnormally low blood pressure. His keen observation led to the development of the famous sublingual nitroglycerin pills , administered as an emergency vasodilator in the event of a heart attack.
Since then, and until Moncada’s revolutionary discovery, no one could suspect that NO was produced naturally by the cells of many organisms for more than 500 million years , constituting one of the most successful molecular messengers in evolution.
Looking inside the cell
Nitric oxide is synthesized within cells from the amino acid L-arginine with the help of a protein, NO-synthase . The gas quickly diffuses through cell membranes and in less than 30 seconds it is inactivated or destroyed.
It is a short but intense life, in which it plays very different roles depending on the concentration, the tissue and the chemical environment where it occurs: from protector against free radicals or precursor of some of the most toxic ones, to innocuous messenger between cells or powerful chemical weapon against invading organisms or tumors.
NO-synthase is expressed in several types of cells with very different objectives: in the endothelium, the cell layer that lines the interior of the arteries, NO is released to induce the contraction of the arterial muscle and cause dilation of the vessels. In this way, NO controls blood pressure and prevents the formation of thrombi. In neurons, NO diffuses rapidly in all directions and over short distances, activating only cells in close proximity. This mechanism is involved in many processes, from learning or sleep to intestinal motility, pain or drug addiction. In white blood cells, the production of high amounts of NO acts as a chemical weapon that destroys bacteria, parasites or tumor cells.
That’s how powerful nitric oxide is.
