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Drug for Chest Pain May Promote Vessel Damage

Nitroglycerin Use Linked to Production of Free Radicals
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WebMD Health News

Feb. 6, 2004 - It has been well over a century since doctors learned that nitroglycerin was useful for relieving the crushing chest pain known as angina that often occurs with coronary artery disease. The treatment is still widely used today, but a new study suggests it may ultimately hurt heart patients more than it helps them.

Researchers say long-term nitroglycerin use appears to promote the production of unstable molecules known as free radicals, which have been implicated in the advancement of heart disease. The concern is that the drug's pain relieving benefit comes at the price of making the patient's heart condition worse.

"This is a drug that has been around forever, and it has just been assumed to be safe," Duke University professor of medicine Jonathan Stamler, MD, tells WebMD. "Our findings and those of others suggest a real need to take a fresh look at it."

Drug Tolerance

Nitroglycerin relieves chest pain by opening constricted blood vessels, allowing more oxygen-rich blood to flow to the heart. But patients quickly build up tolerance to the drug if used for long periods of time.

It was their efforts to identify the cause of this tolerance that led Stamler and colleagues to conclude that the drug may promote blood vessel damage. Two years ago, the research team identified a compound that holds the key to the drug's ability to dilate blood vessels and relieve chest pain. The compound resides in a part of the cell known as the mitochondria.

In lab studies, they found that exposure to high doses of nitroglycerin not only decreased the activity of this compound, but it also damaged the mitochondria. This, in turn, resulted in the increased production of free radicals -- unstable molecules that can damage heart cells and blood vessel walls. The findings are published in the February issue of The Journal of Clinical Investigation.

"Typically when people become tolerant to this drug, the response is to push the dosage higher," Stamler says. "But if we now understand that this tolerance is associated with the production of the same free radicals that have been implicated in cardiovascular disease, this strategy does not make sense."

More Study Needed

In an accompanying editorial, cardiologist John D. Parker, MD, notes that other recent studies have also questioned the long-term safety of nitrate therapy.

"Taken together, these observations suggest that the time has come to mount an appropriately powered clinical trial examining the efficacy and safety of sustained therapy with organic nitrates," he writes.

In the meantime, Stamler says he believes clinicians should rethink their reliance on nitroglycerin, especially among heart patients who also have other medical conditions such as diabetes.

"I would argue that there is enough evidence to at least say that the doses we are using are too high," he says. "Overall, we need to look much more carefully at how we use this drug."

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