The findings bolster earlier indications that the drug may be ineffective for certain patients, and may place others at risk, the researchers said. The results also suggest that certain other drugs should be avoided by heart patient's taking the blood vessel dilator, as those drugs' activity might counteract nitroglycerin's effects. Such 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, said the researchers.
The researchers found through studies in mice that the cellular powerhouses -- known as 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.
Nitroglycerin loses its effects on blood flow in animals lacking a particular mitochondrial enzyme called aldehyde dehydrogenase (mtALDH), the Duke team reported in the August 23, 2005, Proceedings of the National Academy of Sciences (published early online the week of August 15).
"Doctors have prescribed nitroglycerin for the relief of chest pain for some 150 years, yet the mechanism by which the drug works has remained a matter of debate," said study author Jonathan Stamler, M.D., at Duke. "The findings confirm that mtALDH is critical for nitroglycerin action."
"The results should bring closure to long-standing scientific controversy, and will likely change the way physicians deliver nitroglycerin therapy to patients,"
Contact: Kendall Morgan
Duke University Medical Center