Endothelin Drugs Benefit Those With Pulmonary Hypertension PDF Print E-mail
Thursday, 10 September 2009 10:42
taken from http://commons.wikimedia.org/wiki/File:1EDN_human_endothelin1_02.pngBreaking news from Genetic Engineering & Biotechnology has reported that recent research to block the effects of endothelin, a powerful substance that constricts blood vessels and stimulates cell growth, has led to successful treatment of pulmonary arterial hypertension and provides hope for treating other chronic diseases. The usefulness of the new drugs to treat congestive heart failure is much less clear, according to Professor Matthias Barton, M.D. of the Department of Medicine at the University of Zurich School of Medicine.

Endothelin's importance in both health and disease quickly became clear after researchers first discovered its receptors in the early 1990s. The human body continuously produces endothelin and increases its production in response to disease conditions, such as inflammation, high blood pressure or high cholesterol. Nitric oxide, a substance also released from the endothelium that dilates the blood vessels (vasodilator), helps counterbalance endothelin production. Endothelin helps regulate cell growth, contributes to heart muscle contractility and helps determine heart rate. That is only a partial list, and it is all beneficial. On the negative side, endothelin can disturb heart rhythm and promote unfavorable changes in the heart muscle following congestive heart failure. Endothelin also promotes kidney disease and coronary artery disease, among other disorders.

Clininal trials have begun to use endothelin receptor antagonists to treat pulmonary hypertension, resistant arterial hypertension, proteinuric renal disease, cancer and autoimmune diseases such as Scleroderma. The following are some research highlights on endothelin receptor antagonists:

Pulmonary Hypertension. The FDA has approved the use of endothelin blockers to treat human pulmonary hypertension which is a disease with a poor prognosis. The first clinical trials have demonstrated benefits regarding symptoms and have improved the quality of life of the patients. These drugs targeted either the ETA receptor alone, or both receptors, ETA and ETB, together.

Proteinuric Renal Disease. Protein excretion in the urine is a reliable predictor of cardiovascular risk. According to the first clinical studies treatment with drugs that block ETA alone, and treatment with drugs that blocks both receptors, reduced protein excretion in the urine in patients with renal failure, even in patients already treated with other anti-proteinuric drugs.

Coronary Artery Disease. Research on mice with atherosclerosis (hardening of the arteries from plaque buildup) has found that inhibiting endothelin inhibits the development of atherosclerotic plaque. Also in mice, blocking the ETA receptor alleviates some of the causes leading to angina and can reduce damage to the heart tissue following a heart attack. Finally, chronic treatment with an ETA receptor improves the ability of blood vessels to dilate.

Resistant Arterial hypertension. Treatment with a drug that blocks ETA alone, and treatment with a drug that blocks both receptors, substantially reduced arterial blood pressure in human patients with essential or resistant essential hypertension. Further research is necessary to determine whether the drugs can reduce hypertension-related organ damage such as failure of the heart or kidneys or the number of deaths associated with hypertension.

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