UMDNJ Researcher Discovers Potential Cause for
Tolerance to Nitroglycerin in Treatment of Cardiovascular Diseases
NEWARK — A researcher at The University of Medicine and Dentistry of New Jersey-New Jersey Medical School may have unlocked the secret to why patients with some types of cardiovascular diseases become resistant to the blood vessel-relaxing effect of nitric oxide.
Nitric oxide is more commonly known as a toxic air pollutant by automobile engines and power plants, but it is also made by the body, acting as a catalyst for blood flow. The relaxation of blood vessels through the dispensing of nitroglycerin, a clinically used substance that generates nitric oxide, is essential to lowering the blood pressure of patients suffering from chest pain. Prolonged exposure to nitroglycerin, however, has shown to be ineffective.
Annie Beuve, Ph.D., assistant professor of Pharmacology and Physiology, was the senior author of a study that identifies nitric oxide as altering a binding molecule, a protein called soluble guanylyl cyclase. Beuve speculates it is this modification by nitric oxide that could explain why the blood vessels stop relaxing after repeated stimulation and that this process could take place during the development of cardiovascular diseases including hypertension and atherosclerosis, a disease affecting the arterial blood vessels.
Understanding its mechanism will help develop new strategies for the clinical treatment of these diseases which affect more than 50 million Americans. Beuve teamed up with Focco van den Akker, PhD, assistant professor of Biochemistry at Case Western Reserve University, to discover the molecular mechanism by which nitric oxide alters soluble guanylyl cyclase properties. Their findings appeared in a recent issue of the Proceedings of the National Academy of Sciences, USA.
“This is an initial step and we need to show that nitroglycerin itself modifies the soluble guanylyl cyclase,” Beuve said. “This will provide new means to prevent development of tolerance. For example, we can try to block the modifications of soluble guanylyl cyclase thereby maintaining the relaxation and sensitivity of the blood vessels.”
In January, Beuve and van Den Akker initiated their research on the stimulation of soluble guanylyl cyclase by nitric oxide and its relation to development of cardiovascular diseases. At that time, van den Akker and Beuve clarified the means by which nitric oxide and carbon monoxide bind to the protein, which induces the relaxation of blood vessels.
Media interested in interviewing Beuve should contact Terri Guess at 973-972-5000.
UMDNJ is the nation's largest free-standing public health sciences university with more than 5,500 students attending the state's three medical schools, its only dental school, a graduate school of biomedical sciences, a school of health related professions, a school of nursing and its only school of public health, on five campuses. Last year, there were more than two million patient visits to UMDNJ facilities and faculty at campuses in Newark, New Brunswick/Piscataway, Scotch Plains, Camden and Stratford. UMDNJ operates University Hospital, a Level I Trauma Center in Newark, and University Behavioral HealthCare, a mental health and addiction services network.