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MR antagonists have been a key therapy for attenuating the pathologic effects of aldosterone but are associated with some side effects and may not always adequately attenuate the nongenomic effects of aldosterone. Aldosterone is primarily synthesized by the CYP11B2 aldosterone synthase enzyme, which is very similar in structure to other enzymes involved in steroid biosynthesis including CYP11B1, a key enzyme involved in glucocorticoid production. Lack of specificity for CYP11B2, off-target effects on the hypothalamic-pituitary-adrenal axis, and counterproductive increased levels of bioactive steroid intermediates such as 11-deoxycorticosterone have posed challenges in the development of early aldosterone synthase inhibitors such as osilodrostat. In early-phase clinical trials, newer aldosterone synthase inhibitors demonstrated promise in lowering blood pressure in patients with treatment-resistant and uncontrolled hypertension. It is therefore plausible that these agents offer protection in other disease states including heart failure or chronic kidney disease. Further clinical evaluation will be needed to clarify the role of aldosterone synthase inhibitors, a promising class of agents that represent a potentially major therapeutic advance. <\/jats:p>","DOI":"10.1152\/ajpheart.00419.2023","type":"journal-article","created":{"date-parts":[[2023,12,22]],"date-time":"2023-12-22T15:29:06Z","timestamp":1703258946000},"page":"H670-H688","update-policy":"https:\/\/doi.org\/10.1152\/aps-crossmark-policy","source":"Crossref","is-referenced-by-count":66,"title":["Aldosterone and aldosterone synthase inhibitors in cardiorenal disease"],"prefix":"10.1152","volume":"326","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4018-8533","authenticated-orcid":false,"given":"Subodh","family":"Verma","sequence":"first","affiliation":[{"name":"Division of Cardiac Surgery, St. Michael\u2019s Hospital\u2013Unity Health Toronto, Toronto, Ontario, Canada"},{"name":"Department of Surgery, University of Toronto, Toronto, Ontario, Canada"},{"name":"Department of Pharmacology and Toxicology, University of Toronto, Toronto, Ontario, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Avinash","family":"Pandey","sequence":"additional","affiliation":[{"name":"Department of Medicine, University of Ottawa, Ottawa, Ontario, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arjun K.","family":"Pandey","sequence":"additional","affiliation":[{"name":"Department of Medicine, University of Toronto, Toronto, Ontario, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Javed","family":"Butler","sequence":"additional","affiliation":[{"name":"Baylor Scott and White Research Institute, Dallas, Texas, United States"},{"name":"University of Mississippi, Jackson, Mississippi, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John S.","family":"Lee","sequence":"additional","affiliation":[{"name":"LJ Biosciences, LLC, Rockville, Maryland, United States"},{"name":"PhaseBio Pharmaceuticals, Malvern, Pennsylvania, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1036-4767","authenticated-orcid":false,"given":"Hwee","family":"Teoh","sequence":"additional","affiliation":[{"name":"Division of Cardiac Surgery, St. Michael\u2019s Hospital\u2013Unity Health Toronto, Toronto, Ontario, Canada"},{"name":"Division of Endocrinology and Metabolism, St. Michael\u2019s Hospital\u2013Unity Health Toronto, Toronto, Ontario, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2566-4308","authenticated-orcid":false,"given":"C. 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