Dynamite discovery on nitroglycerin

Nitroglycerin’s talent for opening blood vessels, now frequently exploited by doctors treating people with angina or heart failure, was first observed in the 1860s when physicians studied side effects experienced by workers in a dynamite factory. Scientists have now found a long-sought enzyme that may be behind nitroglycerin’s dilation of blood vessels.

In work that led to a Nobel prize in 1998, investigators several decades ago learned that nitroglycerin’s medicinal effects are the result of its conversion in the body into nitric oxide (SN: 10/17/98, p. 246). This gas relaxes the muscle cells that narrow and expand blood vessels.

Because it’s difficult to grow blood vessels in the laboratory, investigators have struggled to identify the molecules that convert nitroglycerin into nitric oxide.

Seeking tissues that are easier to study, Jonathan S. Stamler of Duke University Medical Center in Durham, N.C., and his colleagues recently found that immune cells called macrophages perform the chemical trick.

In an upcoming Proceedings of the National Academy of Sciences, the researchers identify an enzyme that begins the breakdown of nitroglycerin. The enzyme, aldehyde dehydrogenase, is normally employed for other purposes by mitochondria, which are the energy-generating organelles within cells.

According to test-tube studies, the enzyme becomes depleted inside macrophages exposed to nitroglycerin for a long period. This may explain why the drug becomes ineffective over time in some people. By robbing mitochondria of a needed enzyme, nitroglycerin may also cause cellular damage in the long run, the scientists speculate. That may be why there’s no proof that nitroglycerin improves the prognosis of heart patients and why some data indicate that the drug actually exacerbates a patient’s condition.