The medical uses about Endothelin 1

Endothelin 1 transcript is constitutively destabilized by its 3'-UTR through two destabilizing elements, DE1 and DE2. DE1 functions through a conserved ARE by the AUF1-proteasome pathway and is regulated by the heat shock pathway. In a healthy individual, a delicate balance between vasoconstriction and vasodilation is maintained by endothelin and other vasoconstrictors on the one hand and nitric oxide, prostacyclin and other vasodilators on the other.

Overproduction of endothelin in the lungs may cause pulmonary hypertension, which can sometimes be treated by the use of an endothelin receptor antagonist, such as bosentan, sitaxentan or ambrisentan. The latter drug selectively blocks endothelin A receptors, decreasing the vasoconstrictive actions and allowing for increased beneficial effects of endothelin B stimulation, such as nitric oxide production. The precise effects of endothelin B receptor activation depends on the type of cells involved.

Because of its powerful vasoconstrictor properties, and its effects on intracellular calcium, ET-1 has been implicated in the pathogenesis of hypertension, coronary vasospasm, and heart failure. In the latter condition, Endothelin 1 is released by the failing myocardium where it can contribute to calcium overload and hypertrophy. Endothelin  receptor antagonists have been shown to decrease mortality and improve hemodynamics in experimental models of heart failure. A number of studies suggest a role for ET-1 in pulmonary hypertension, as well as in systemic hypertension. A non-selective Endothelin 1 receptor antagonist (bosentan) is currently used in the treatment of pulmonary hypertension.

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