When nitroglycerin is used as a medication for chest pain and heart disease for prolonged periods, its effectiveness is often diminished.
A critical finding that was revealed by scientists at the University of Medicine and Dentistry of New Jersey may hold the answer to more effective treatments. Research outcomes were published recently in the prestigious international cardiovascular journal entitled Circulation Research.
Annie Beuve, Ph.D., associate professor of Pharmacology and Physiology, and Walter Duran, Ph.D., professor of the Department of Pharmacology and Physiology and the Department of Surgery, both of the UMDNJ-New Jersey Medical School, were collaborators on this study. Since the 19th century, nitroglycerin has been used to relax blood vessels and increase blood flow in patients who show symptoms related to cardiovascular disease. After 24 hours of continuous treatment, patients experience "nitrate tolerance." Blood vessels then become resistant to nitroglycerin rendering the treatment inefficient.
"Clinically, our discovery can help us design therapeutic strategies to overcome the loss of sensitivity to nitroglycerin, a widely prescribed treatment for cardiovascular disease. We aim to help improve the quality of life for 70 million Americans who live with heart disease," said Beuve.
The reason for this insensitivity to the drug has remained a mystery for more than 100 years. Beuve and Duran's study shows nitroglycerin modifies a key molecule called soluble guanylyl cyclase, which is a fundamental mediator in the relaxation of blood vessels. They believe anti-oxidants may help prevent nitroglycerin from modifying soluble guanylyl cyclase, thereby allowing patients a longer treatment course and more efficient therapy for CVD. Other co-authors of the article, 'Nitroglycerin-Induced S-nitrosylation and desensitization of soluble guanylyl cyclase contribute to nitrate tolerance,' are: Sayed N, Kim DD, Fioramonti X, Iwahashi T, Durán WN, Beuve A.