{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,3]],"date-time":"2026-07-03T21:48:57Z","timestamp":1783115337683,"version":"3.54.6"},"reference-count":134,"publisher":"SAGE Publications","issue":"5","license":[{"start":{"date-parts":[[2014,7,1]],"date-time":"2014-07-01T00:00:00Z","timestamp":1404172800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["Therapeutic Advances in Cardiovascular Disease"],"published-print":{"date-parts":[[2014,10]]},"abstract":"<jats:p> Endothelin 1 (ET-1), a potent vasoconstrictive substance, was discovered in 1988 by Yanagisawa and colleagues, and since then, a quarter of a century has passed. Understanding the biology of ET-1 has rapidly developed by characterizing the components of its receptors and processing enzymes. Numerous studies have revealed not only physiological but also various pathophysiological roles of the ET system. At first, ET-1 was the attractive and promising target for the treatment of hypertension owing to its potent vasoconstrictive nature and a variety of ET receptor antagonists (ERAs) were studied. However, the clinical application to treat hypertension was disappointing because of the side effects, including liver toxicity and fluid retention. On the other hand, ERAs have been established as orphan drugs for the treatment of pulmonary arterial hypertension and improved the prognosis of patients. Furthermore, multipotency of the ET system in the pathogenesis of multiple diseases has led to the development of translational research not only in the field of hypertension but in a variety of fields. Furthermore, a range of studies are ongoing to apply ERAs to clinical situations. In this article, we review the pathophysiological roles of the ET system in hypertension and pulmonary hypertension and the potential of ET receptor antagonism for the treatment of these diseases. <\/jats:p>","DOI":"10.1177\/1753944714541511","type":"journal-article","created":{"date-parts":[[2014,7,3]],"date-time":"2014-07-03T05:42:40Z","timestamp":1404366160000},"page":"202-216","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":36,"title":["Current state of endothelin receptor antagonism in hypertension and pulmonary hypertension"],"prefix":"10.1177","volume":"8","author":[{"given":"Kazuya","family":"Miyagawa","sequence":"first","affiliation":[{"name":"Division of Cardiovascular Medicine, Department of Internal Medicine, Kobe University Graduate School of Medicine, Kobe, 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