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| Chemist Ascanio Sobrero |
@HealthMed Glyceryl
trinitrate - GTN (discovered by Italian chemist Ascanio Sobrero in 1846-1847) - is widely used to prevent or reduce
angina, a key warning symptom of coronary heart disease.
An early clue
that GTN might have medicinal properties came from the observation that
handling the chemical could result in severe headache. GTN is also known
as nitroglycerine, an important component in early explosives. Workers in early munitions factories developed vascular headaches. And quarrymen handling nitroglycerine-based explosives were also at risk of
such severe headaches that resignation may have been preferrable to recurrent onset of these severe symptoms.
This lead to
trials of GTN in angina by Dr William Murrell, with publication of results in 1879 in the UK medical journal The Lancet, followed by increasing popularity in use of
GTN as treatment.
The major
beneficial effects of GTN are due to relaxation of veins, so reducing the
filling pressure in the heart. This in turn, through Starling's Law of the Heart, reduces the work of the main pumps of the heart, the ventricles. Nitric oxide is a vasodilator made in the body
by the cells that line blood vessels, endothelial cells: work on this pathway
resulted in the award of the Nobel Prize in Physiology or
Medicine for 1998 to Robert F Furchgott, Louis
J Ignarro and Ferid
Murad for their discoveries concerning "the nitric oxide as a
signalling molecule in the cardiovascular system".
Anti-anginal effects of GTN result from the
dilator response of veins to the additional nitric oxide generated from the GTN
by vascular enzymes (including mitochondrial aldehyde dehydrogenase). And
this effect on veins occurs at a lower concentration of the drug than needed to
relax arteries. Headache as an unwanted side effect of the drug is due to
an increase in blood flow in arteries in the head. The chance of arterial
headache developing can thus be minimised by spitting out any remaining GTN
once angina has settled.
Footnote
There had been an earlier report in The Lancet in 1867 by Dr T. Lauder Brunton from Edinburgh on use of an organic nitrite, amyl nitrite, to treat angina. There is now evidence that nitrite may act as a chemical signal, independent of its vasodilator and other effects through conversion to nitric oxide.
William Murrell's 1879 Lancet paper.
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