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Cardiovascular Discovery Is Highlighted in Prestigious Scientific Journal E-mail
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Researchers at UMDNJ have discovered cause of "nitrate tolerance" in patients taking nitroglycerin medication over an extended period of time to treat chest pain caused by heart disease.

The effectiveness of nitroglycerin is often diminished when used as a medication for chest pain and heart disease for prolonged periods. 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.

About UMDNJ-New Jersey Medical School

Founded in 1954 as the Seton Hall College of Medicine and Dentistry, the New Jersey Medical School was the state's first medical school. Today, it is part of the University of Medicine and Dentistry of New Jersey. NJMS has four mission areas: education, research, clinical care, and community outreach. It has 21 departments and more than 70 centers and institutes. In addition to offering the MD degree to its students, NJMS also offers, MD/PhD, MD/MPH, and MD/MBA degrees through collaborations with other institutions of higher education.

University of Medicine and Dentistry of New Jersey (UMDNJ)

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.

About Heart Disease

Heart disease is a broad term that includes several more specific heart conditions. These conditions include:

  • Arrhythmias. Irregular, or abnormally fast or slow, beating of the heart. The heart beat is controlled by electrical impulses. When the timing or frequency of these electrical impulses are disrupted, arrhythmias develop. Some arrhythmias are quite serious. An example is ventricular fibrillation, a severely abnormal heart rhythm that causes death unless treated right away by providing an electrical shock to the heart (called defibrillation). Others are less severe but can develop into more serious conditions over time. A particular concern is atrial fibrillation. Atrial fibrillation is rapid, irregular beating of the upper chambers of the heart. The chambers can quiver instead of beating in a regular pattern. Blood is not fully pumped out of them and may pool and clot.

  • Cardiomyopathy. A weakening of the heart muscle or a change in heart muscle structure. It often results in inadequate heart pumping or other heart function abnormalities. These can result from various causes, including prior heart attacks, viral or bacterial infections, and others.

  • Congenital Heart Disease. Malformations of heart structures, present during pregnancy or at birth. These may be caused by genetic factors or by adverse exposures during pregnancy. Examples include holes in the walls that divide the heart chambers, abnormal heart valves, and others. Congenital heart defects can disrupt the normal flow of blood through the heart. Congenital heart defects are the most common type of major birth defect.

  • Coronary Heart Disease (CHD). CHD is the most common type of heart disease. CHD occurs when the coronary arteries, that supply blood to the heart muscle, become hardened and narrowed due to the plaque buildup. The plaque buildup and the narrowing and hardening of the arteries is called atherosclerosis. Plaques are a mixture of fatty substances including cholesterol and other lipids. Blood flow and oxygen supply to the heart can be reduced or even fully blocked with a growing plaque. Plaques may also rupture and cause blood clots that block arteries. CHD can lead to a heart attack. Angina, the most common symptom of CHD can also occur. Angina is chest pain or discomfort that occurs when the heart muscle is not getting enough blood. Irregular heart beats, called arrhythmias, can develop. Over time, CHD can weaken the heart muscle and lead to heart failure, a serious problem where the heart cannot pump blood the way that it should.

  • Heart Attack. A heart attack, also called a myocardial infarction may occur when blood supply to the heart is severely reduced or completely blocked. When blood flow is restricted the heart muscle cells do not receive enough oxygen and begin to die. The more time that passes without treatment to restore blood flow, the greater the damage to the heart. This damage can cause irregular heart rhythms or even sudden cardiac arrest or stopping of the heart beat. Death can result. Coronary artery disease is the chief underlying cause of a heart attack. A less common cause of a heart attack is a severe spasm of a coronary artery that reduces the blood supply to the heart.

  • Heart Failure. This may also be called congestive heart failure or chronic heart failure. Heart failure is a condition where the heart cannot pump enough blood and oxygen to meet the needs of other body organs. Heart failure does not mean that the heart has stopped, but that it cannot pump blood the way that it should. Heart failure is a serious condition. There is no cure for heart failure at this time, except a heart transplant. Once diagnosed, medicines are needed for the rest of the person's life. See our heart failure fact sheet.

  • Peripheral Arterial Disease (PAD). Hardening of the arteries that supply blood to the arms and legs. PAD is usually the result of atherosclerosis, the buildup of plaque and narrowing of the arteries. Blood flow and oxygen to the muscles in the arms and legs can be reduced or even fully blocked. Painful leg muscles, numbness, swelling in the ankles and feet, and weak pulse in the feet are some of the signs and symptoms of PAD.

  • Rheumatic Heart Disease. This condition is damage to the heart valves and other heart structures due to inflammation and scarring caused by rheumatic fever, which occurs from streptococcal infection. Heart disease is an umbrella term for a number of different diseases affecting the heart. Heart disease is a number of abnormal conditions affecting the heart and the blood vessels in the heart.

 

 
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