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The mystery began over 100 years ago when workers who had heart problems in Alfred Nobel's dynamite factory reported that being on the job improved their chest pain, but that they were experiencing headaches.
Scientists eventually realized that nitroglycerine--one of the compounds used to make dynamite--was dilating blood vessels. The effect helped the heart, but caused throbbing pain in the brain.
Nitroglycerine quickly became standard drug therapy for angina, and it has remained so ever since. Its one problem has been that, for unknown reasons, patients develop a tolerance to the drug and doctors must stop treatment for a while.
Now researchers at Duke University Medical Center say they have identified the enzyme responsible for nitroglycerine's effects, where the enzyme works, and why the effects wear off.
Dr. Jonathan Stamler and his team report that the enzyme does its work in cell components called mitochrondria that convert food to energy. The enzyme, called mitochondrial aldehyde dehydrogenase, becomes depleted after repeated exposure to nitroglycerin, blocking its effect and even damaging heart cells.
The new research opens the way to better drugs that could have benefits of nitroglycerine without its drawbacks.
"We have made some different molecules that we think should work and that won't inhibit the enzyme in the same way," said Dr. Stamler. "Also, we have a new class of drugs, nitrate derivatives, that we believe can be used in other parts of the body and won't have this problem."
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