Nitroglycerin May Increase Cardiovascular Risk

Researchers have discovered that in rats treated with nitroglycerin for a period of three days, the activity of a key enzyme declined, and mitochondria lacking the enzyme activity due to prolonged use of the drug began producing free radicals that could damage heart cells and blood vessel walls. These results were reported in the February 1, 2004, issue of the Journal of Clinical Investigation.

Rats treated with nitroglycerin for three days demonstrated tolerance to the drug, as shown by the failure of the drug to decrease blood pressure by dilating blood vessels. The rats exhibited a significant decline in activity of mitochondrial aldehyde dehydrogenase (ALDH-2), the enzyme crucial to nitroglycerin's beneficial effects. As a result, treatment of blood vessels with other substances known to block ALDH-2 activity had little effect. As ALDH-2 declined with further nitroglycerin treatment, mitochondria in the heart cells of rats greatly increased the production of free radicals. Treatment with antioxidants reduced the production of these and restored activity of the ALDH-2 enzyme.

"Nitroglycerin is one of the most commonly used drugs in the western world,” said Jonathan Stamler, M.D., a Howard Hughes Medical Institute investigator at Duke University Medical Center (Durham, NC, USA; www.mc.duke.edu), who headed an international team of researchers. "Our findings raise concern that the drug may have deleterious consequences. The drug's long-term effects on patients should be re-examined in clinical trials and, in the meantime, physicians should use caution and lower the dose prescribed to patients.”




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