Abstract
The endothelin axis, recognized for its vasoconstrictive action, plays a central role in the pathology of pulmonary arterial hypertension (PAH). Treatment with approved endothelin receptor antagonists (ERAs), such as bosentan, ambrisentan, or macitentan, slow down PAH progression and relieves symptoms. Several findings have indicated that endothelin is further involved in the pathogenesis of certain other diseases, making ERAs potentially beneficial in the treatment of various conditions. In addition to PAH, this review summarizes the use and perspectives of ERAs in cancer, renal disease, fibrotic disorders, systemic scleroderma, vasospasm, and pain management. Bosentan has proven to be effective in systemic sclerosis PAH and in decreasing the development of vasospasm-related digital ulcers. The selective ERA clazosentan has been shown to be effective in preventing cerebral vasospasm and delaying ischemic neurological deficits and new infarcts. Furthermore, in the SONAR (Study Of Diabetic Nephropathy With Atrasentan) trial, the selective ERA atrasentan reduced the risk of renal events in patients with diabetes and chronic kidney disease. These data suggest atrasentan as a new therapy in the treatment of diabetic nephropathy and possibly other renal diseases. Preclinical studies regarding heart failure, cancer, and fibrotic diseases have demonstrated promising effects, but clinical trials have not yet produced measurable results. Nevertheless, the potential benefits of ERAs may not be fully realized.
Highlights
The endothelin axis is most recognized for its potent vasoconstrictive action involved in the physiological regulation of vascular tone
In addition to pulmonary arterial hypertension (PAH), this review summarizes the use and perspectives of endothelin receptor antagonists (ERAs) in cancer, renal disease, fibrotic disorders, systemic scleroderma, vasospasm, and pain management
Atrasentan significantly reduced the risk of renal events in the selected patients with diabetes and chronic kidney disease (CKD) compared to placebo [142], and the results represented one of the first successful trials of therapeutics that target the kidney in diabetes patients in more than 10 years [138]
Summary
The endothelin axis is most recognized for its potent vasoconstrictive action involved in the physiological regulation of vascular tone. The overproduction of endothelin in the lung can cause pulmonary arterial hypertension (PAH). Endothelin receptor antagonists (ERAs) have been approved for the treatment of this disease [1]. The endothelin axis has pleiotropic functions associated with fundamental cellular processes, including cell proliferation and apoptosis. The ubiquitous distribution of endothelin and its receptors implicates their involvement in a wide variety of physiological and pathological processes among different organ systems [9]. Chronic endothelin stimulation has been implicated in several human cardiovascular, inflammatory, fibrogenic and oncologic diseases [1,10]. Pharmaceutical agents that act on the endothelin axis might be beneficial in the treatment of numerous and diverse diseases [1]. This review will discuss the use and benefits of ERAs in PAH and beyond
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
