Only 10 years ago, the vasoconstricting peptide endothelin was discovered; it is produced by endothelial cells. Different isoforms and receptors of endothelin have been identified. The effects of endothelin-I, the most important isoform, are mainly vasoconstriction and proliferation of cells. In the last few years endothelin receptor antagonists have become available, which can delineate the clinical importance of the endothelin system. Possible indications for endothelin receptor blockers are renal disease (acute and chronic renal failure) and cardiovascular disease (heart failure; restenosis after percutaneous transluminal coronary angioplasty (PTCA); pulmonary hypertension; systemic hypertension). There is also a possible role for endothelin receptor blockers in oncology (prostatic carcinoma). Currently clinical trials are being carried out to determine the efficacy of these compounds for the above-mentioned indications.
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Transplant Direct
March 2024
Actelion Pharmaceuticals Ltd, Janssen Pharmaceutical Company of Johnson and Johnson, Global Epidemiology, Allschwil, Switzerland.
Background: Portopulmonary hypertension (PoPH) occurs in patients with advanced liver disease and can be a contraindication to liver transplant (LT). Improvement of hemodynamic parameters with pulmonary arterial hypertension (PAH) therapies (including endothelin receptor antagonists [ERAs]) may help some patients to become eligible for LT.
Methods: We conducted a retrospective secondary data analysis to describe the clinical course and management of PoPH in patients on a US registry LT waitlist and outcomes in patients receiving an ERA.
Clin Kidney J
January 2025
Department of General Internal Medicine and Nephrology, Robert Bosch Hospital Stuttgart, Stuttgart, Germany.
Background: Sparsentan, a dual-acting antagonist for both the angiotensin II receptor type 1 and the endothelin receptor type A, has emerged as a promising therapeutic agent for the treatment of IgA nephropathy (IgAN). Following the publication of the PROTECT trial, sparsentan recently received approval for the treatment of IgAN in Europe. However, it remains uncertain whether an additive effect can be observed in the context of existing treatment with sodium-glucose co-transporter 2 (SGLT2) inhibitors, given that the PROTECT study did not investigate this dual therapy approach.
View Article and Find Full Text PDFNaunyn Schmiedebergs Arch Pharmacol
January 2025
Department of Physiology, College of Medicine, King Saud University, 12271, Riyadh, Saudi Arabia.
Ischemia-reperfusion injury (IRI) is a common pathogenic situation that arises throughout all liver surgeries, including liver transplants. We aimed to compare the preventive effects of valsartan (VST) against valsartan + sacubitril (LCZ696) on hepatic injury caused by IRI. A total of thirty-six male Westar albino rats were split into six groups randomly: sham, IRI, VST + IRI, LCZ696 + IRI, VST, and LCZ696.
View Article and Find Full Text PDFiScience
January 2025
Department of Regenerative Medicine and Cell Biology, Medical University of South Carolina, Charleston, SC 29425, USA.
Mutations in the human genes encoding the endothelin ligand-receptor pair and cause Waardenburg-Shah syndrome (WS4), which includes congenital hearing impairment. The current explanation for auditory dysfunction is defective migration of neural crest-derived melanocytes to the inner ear. We explored the role of endothelin signaling in auditory development in mice using neural crest-specific and placode-specific mutation plus related genetic resources.
View Article and Find Full Text PDFRev Cardiovasc Med
January 2025
Department of Cardiovascular Medicine, Beijing Hospital, National Center of Gerontology, Institute of Geriatric Medicine, Chinese Academy of Medical Sciences, 100730 Beijing, China.
Background: Hypertension is one of the most prevalent disorders encountered in medical practice, yet effective pharmacotherapy options for resistant hypertension are limited. In this meta-analysis, we aimed to evaluate the efficacy and safety of aprocitentan in treating hypertension.
Methods: We searched PubMed, Embase, ClinicalTrials.
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