Treatment of pulmonary arterial hypertension with the endothelin receptor antagonist bosentan has been associated with transient increases in liver transaminases. Mechanistically, bosentan inhibits the bile salt export pump (BSEP) leading to an intrahepatic accumulation of cytotoxic bile salts, which eventually results in hepatocellular damage. BSEP inhibition by bosentan is amplified by its ac...

BACKGROUND & AIMS Endothelins are expressed in many enteric neurons of the gut. Because activation of endothelin ET(A) and ET(B) receptors is known to alter intestinal muscle activity, the effect of ET(A) and ET(B) receptor agonists and antagonists on propulsive peristalsis was examined. METHODS Repetitive peristalsis in fluid-perfused segments of the guinea pig isolated small intestine was e...

Evidence has accumulated showing that vasoactive peptides, such as endothelin-1, adrenomedullin and urotensin-II, are expressed in various kinds of tumour cells. In the present study, the expression of endothelin-1 and endothelin receptors was studied in eight human tumour cell lines: T98G (glioblastoma), IMR-32 and NB69 (neuroblastoma), BeWo (choriocarcinoma), SW-13 (adrenocortical carcinoma),...

Ambrisentan (Letairis; Gilead Sciences, Foster City, CA) is an endothelin receptor antagonist approved by the U.S. Food and Drug Administration for the treatment of pulmonary arterial hypertension. The authors describe the occurrence of bilateral cotton wool spots soon after initiation of ambrisentan treatment in a 29-year-old woman. Fluorescein angiography, optical coherence tomography, and fu...

Various Gq protein-coupled receptor agonists such as the alpha1 adrenoceptor agonist phenylephrine, angiotensin II, and endothelin-1 are potent hypertrophic factors. There is evidence of potential cross talk between these agents, particularly in terms of endothelin-1 as playing a central role in mediating the actions of other hypertrophic factors. Using cultured rat neonatal ventricular myocyte...

Major limitations of pulmonary arterial hypertension (PAH) drug trials include the small number of enrolled patients, short term follow up (12-16 weeks), and lack of morbidity and mortality primary endpoints. The recently published SERAPHIN (Study with an Endothelin Receptor Antagonist in Pulmonary arterial Hypertension to Improve cliNical outcome) trial represents an important landmark in the ...

Gorman, Mark W., Martin Farias III, Keith N. Richmond, Johnathan D. Tune, and Eric O. Feigl. Role of endothelin in -adrenoceptor coronary vasoconstriction. Am J Physiol Heart Circ Physiol 288: H1937–H1942, 2005. First published December 9, 2004; doi:10.1152/ajpheart.01076.2004.—It has been proposed that -adrenoceptor vasoconstriction in coronary resistance vessels results not from -adrenoceptor...