Cautions on Nitroglycerin Use

While heart patients have long appreciated the pain relief brought by nitroglycerin tablets, researchers have just as long puzzled over how the drug works. Now professor of medicine Jonathan Stamler and his colleagues have pinpointed the active mechanism of nitroglycerin.

As reported in the August 23 Proceedings of the National Academy of Sciences, the researchers found that the cellular powerhouses called mitochondria break down nitroglycerin to release nitric oxide, thereby opening blood vessels and lowering blood pressure. Nitric oxide normally present in the bloodstream plays a critical role in controlling blood vessel relaxation.

While the scientists' findings shed important light on the drug, they also bring a note of caution. The findings indicate the drug should be prescribed judiciously, since chronic use could damage mitochondria, Stamler says. He adds that physicians should use caution in treating patients such as diabetics, who are already vulnerable to mitochondrial damage. The researchers also cautioned that patients on nitroglycerin should avoid taking other drugs that inhibit activity of the critical mitochondrial enzyme, called mtALDH, which is key to nitroglycerin's action. These drugs include sulfonylureas used by diabetics, chloral hydrates used for sleep disorders, and acetaminophen (e.g., Tylenol). Alcohol may also block the effect of nitroglycerin, the researchers say.

The drug may be less effective for patients with particular variants of the mtALDH gene, according to Stamler. He notes that many Asian people carry a mutant version of the gene characterized by reduced mtALDH activity. The lower activity enzyme would leave such patients less responsive to nitroglycerin therapy.

"The results should bring closure to long-standing scientific controversy, and will likely change the way physicians deliver nitroglycerin therapy to patients," says Stamler. "These findings should certainly motivate a reassessment of this class of drugs."