Endothelin drugs helps patients with pulmonary hypertension

Dr. Barton will give an update on endothelin research at the American Physiological Society’s (APS; www.the-aps.org) 11th International Conference on Endothelin. The title of his talk is “What You Should Know About Endothelin,” is part of the symposium, “Roles of Endothelin-1 on Cardiac Function and Diseases.” The conference takes place Sept. 9-12 in Montreal.

What is Endothelin?

Endothelin’s importance in both health and disease quickly became clear after researchers first discovered its receptors in the early 1990s, according to Dr. Barton. It is the most potent and longest lasting of the blood vessel constrictors (vasoconstrictors) and is 100 times more powerful than the vasoconstrictor norepinephrine.

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’s duties are wide ranging. In addition to being a vasoconstrictor, it also 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.

Researchers have recently developed drugs in hopes of blocking the negative effects of the most important form of endothelin, endothelin-1. The drugs, including ambrisentan, bosentan, darusentan, enrasentan, sitaxsentan, and tezosentan are endothelin receptor antagonists. That is, they work by preventing endothelin-1 from linking with one or both of its receptors, ETA and ETB. Endothelin cannot work without at least one of these receptors.

By American Physiological Society