{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T08:52:58Z","timestamp":1791276778070,"version":"4.1.0"},"reference-count":47,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T00:00:00Z","timestamp":1791244800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Cardiovasc. Med."],"abstract":"<jats:p>Mineralocorticoid receptor antagonists (MRAs) serve as a foundational therapies in the management of heart failure, hypertension, and chronic kidney disease. Their primary therapeutic efficacy stems from the competitive antagonism of the mineralocorticoid receptor (MR), which mitigates pathological cascades such as endothelial dysfunction, oxidative stress, chronic inflammation, and perivascular fibrosis. Coronary microvascular dysfunction (CMD)\u2014a pivotal pathological driver across a spectrum of cardiovascular diseases\u2014is defined by impaired vasodilation, heightened microvascular resistance, and diminished coronary flow reserve (CFR). Given that CMD is inextricably linked to dysregulated MR signaling, the restoration of microvascular function represents a key mechanism through which MRAs exert their cardioprotective effects. This review delineates the physiological mechanisms, diagnostic indicators, and generational evolution of MRAs in the context of coronary microcirculation. By synthesizing evidence from animal and clinical studies, this work clarifies the therapeutic utility of MRAs for microvascular protection and provides a comprehensive framework for understanding their pharmacological role in CMD research.<\/jats:p>","DOI":"10.3389\/fcvm.2026.1855673","type":"journal-article","created":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T08:25:22Z","timestamp":1791275122000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Effects of mineralocorticoid receptor antagonists on coronary microcirculation: a mini-review"],"prefix":"10.3389","volume":"13","author":[{"given":"Yu","family":"Li","sequence":"first","affiliation":[{"name":"The First School of Clinical Medicine, Guangdong Medical University","place":["Zhanjiang, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhenhong","family":"Zhang","sequence":"additional","affiliation":[{"name":"The First School of Clinical Medicine, Guangdong Medical University","place":["Zhanjiang, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,10,6]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"100893","DOI":"10.1016\/j.cophys.2025.100893","article-title":"Emerging roles for endothelial mineralocorticoid receptor in disease pathogenesis: potential new indications for mineralocorticoid receptor antagonism","volume":"47","author":"An","year":"2026","journal-title":"Curr Opin Physiol"},{"key":"B2","doi-asserted-by":"publisher","first-page":"585","DOI":"10.1146\/annurev-physiol-060821-013950","article-title":"Roles of mineralocorticoid receptors in cardiovascular and cardiorenal diseases","volume":"84","author":"Barrera-Chimal","year":"2022","journal-title":"Annu Rev Physiol"},{"key":"B3","doi-asserted-by":"publisher","first-page":"3119","DOI":"10.1111\/bph.15708","article-title":"Mineralocorticoid receptor in cardiovascular diseases\u2014clinical trials and mechanistic insights","volume":"179","author":"Bauersachs","year":"2022","journal-title":"Br J Pharmacol"},{"key":"B4","doi-asserted-by":"publisher","first-page":"288","DOI":"10.31083\/j.rcm2508288","article-title":"Navigating the landscape of coronary microvascular research: trends, triumphs, and challenges ahead","volume":"25","author":"Wang","year":"2024","journal-title":"Rev Cardiovasc Med"},{"key":"B5","doi-asserted-by":"publisher","first-page":"373","DOI":"10.1186\/s12872-025-04813-6","article-title":"Prevalence and determinants of apparent treatment-resistant hypertension among patients in South African primary care: a single-centre observational study","volume":"25","author":"Govender","year":"2025","journal-title":"BMC Cardiovasc Disord"},{"key":"B6","doi-asserted-by":"crossref","DOI":"10.1007\/978-1-4614-4887-7","volume-title":"Coronary Vasculature: Development, Structure-function, and Adaptations","author":"Tomanek","year":"2013"},{"key":"B7","doi-asserted-by":"publisher","first-page":"794","DOI":"10.1016\/j.yjmcc.2011.10.001","article-title":"Mechanisms of metabolic coronary flow regulation","volume":"52","author":"Deussen","year":"2012","journal-title":"J Mol Cell Cardiol"},{"key":"B8","doi-asserted-by":"publisher","first-page":"H2100","DOI":"10.1152\/ajpheart.1994.267.6.H2100","article-title":"Morphometry of pig coronary venous system","volume":"267","author":"Kassab","year":"1994","journal-title":"Am J Physiol"},{"key":"B9","doi-asserted-by":"publisher","first-page":"585","DOI":"10.1016\/S0008-6363(96)88626-3","article-title":"Regulation of coronary blood flow: coordination of heterogeneous control mechanisms in vascular microdomains","volume":"29","author":"Jones","year":"1995","journal-title":"Cardiovasc Res"},{"key":"B10","doi-asserted-by":"publisher","first-page":"H443","DOI":"10.1152\/ajpheart.1980.239.4.H443","article-title":"Reference sample microsphere method: cardiac output and blood flows in conscious rat","volume":"239","author":"Ishise","year":"1980","journal-title":"Am J Physiol"},{"key":"B11","doi-asserted-by":"publisher","first-page":"H35","DOI":"10.1152\/ajpheart.1984.247.1.H35","article-title":"Role of site of microsphere injection and catheter position on systemic and regional hemodynamics in rat","volume":"247","author":"Kobrin","year":"1984","journal-title":"Am J Physiol"},{"key":"B12","doi-asserted-by":"publisher","first-page":"645","DOI":"10.1097\/00004872-199605000-00015","article-title":"Losartan reduces cardiac mass and improves coronary flow reserve in the spontaneously hypertensive rat","volume":"14","author":"Kaneko","year":"1996","journal-title":"J Hypertens"},{"key":"B13","doi-asserted-by":"publisher","first-page":"758","DOI":"10.1016\/j.echo.2011.03.010","article-title":"Coronary flow velocity reserve in the three main coronary arteries assessed with transthoracic Doppler: a comparative study with quantitative coronary angiography","volume":"24","author":"Vegsundv\u00e5g","year":"2011","journal-title":"J Am Soc Echocardiogr"},{"key":"B14","doi-asserted-by":"publisher","first-page":"16","DOI":"10.1016\/j.ijcard.2017.08.068","article-title":"International standardization of diagnostic criteria for microvascular angina","volume":"250","author":"Ong","year":"2018","journal-title":"Int J Cardiol"},{"key":"B15","doi-asserted-by":"publisher","first-page":"151","DOI":"10.1016\/S0008-6363(01)00202-4","article-title":"Heterogeneity of resting and hyperemic myocardial blood flow in healthy humans","volume":"50","author":"Chareonthaitawee","year":"2001","journal-title":"Cardiovasc Res"},{"key":"B16","doi-asserted-by":"publisher","first-page":"1041444","DOI":"10.3389\/fcvm.2022.1041444","article-title":"Microcirculation function assessment in acute myocardial infarction: a systematic review of microcirculatory resistance indices","volume":"9","author":"Silva","year":"2022","journal-title":"Front Cardiovasc Med"},{"key":"B17","doi-asserted-by":"publisher","first-page":"3129","DOI":"10.1161\/01.CIR.0000080700.98607.D1","article-title":"Novel index for invasively assessing the coronary microcirculation","volume":"107","author":"Fearon","year":"2003","journal-title":"Circulation"},{"key":"B18","doi-asserted-by":"publisher","first-page":"615","DOI":"10.1016\/j.jacc.2012.11.025","article-title":"Intracoronary enalaPrilat to reduce MICROvascular damage during percutaneous coronary intervention (ProMicro) study","volume":"61","author":"Mangiacapra","year":"2013","journal-title":"J Am Coll Cardiol"},{"key":"B19","doi-asserted-by":"publisher","first-page":"2054","DOI":"10.1161\/CIRCULATIONAHA.105.603522","article-title":"Invasive assessment of the coronary microcirculation: superior reproducibility and less hemodynamic dependence of index of microcirculatory resistance compared with coronary flow reserve","volume":"113","author":"Ng","year":"2006","journal-title":"Circulation"},{"key":"B20","doi-asserted-by":"publisher","first-page":"470","DOI":"10.1016\/j.jcin.2022.12.012","article-title":"Microvascular resistance reserve to assess microvascular dysfunction in ANOCA patients","volume":"16","author":"de Vos","year":"2023","journal-title":"JACC Cardiovasc Interv"},{"key":"B21","doi-asserted-by":"publisher","first-page":"e1714","DOI":"10.1002\/hsr2.1714","article-title":"Coronary microvascular resistance comparison of coronary arteries with and without considering vascular diameter: a retrospective, single-center study","volume":"6","author":"Muroya","year":"2023","journal-title":"Health Sci Rep"},{"key":"B22","doi-asserted-by":"publisher","first-page":"e006194","DOI":"10.1161\/CIRCINTERVENTIONS.117.006194","article-title":"Catheter-based measurements of absolute coronary blood flow and microvascular resistance: feasibility, safety, and reproducibility in humans","volume":"11","author":"Xaplanteris","year":"2018","journal-title":"Circ Cardiovasc Interv"},{"key":"B23","doi-asserted-by":"publisher","first-page":"74","DOI":"10.1007\/s11936-016-0493-3","article-title":"The new frontier of cardiac computed tomography angiography: fractional flow reserve and stress myocardial perfusion","volume":"18","author":"Pontone","year":"2016","journal-title":"Curr Treat Options Cardiovasc Med"},{"key":"B24","doi-asserted-by":"publisher","first-page":"e438","DOI":"10.1002\/mco2.438","article-title":"Chinese expert consensus on the diagnosis and treatment of coronary microvascular diseases (2023 Edition)","volume":"4","author":"Chen","year":"2023","journal-title":"MedComm"},{"key":"B25","doi-asserted-by":"publisher","first-page":"472","DOI":"10.3760\/cma.j.issn.0578-1426.2017.06.017","article-title":"Expert Consensus on Cardiovascular Disease Prevention for Chinese Women","volume":"56","year":"2017","journal-title":"Zhonghua nei ke za zhi"},{"key":"B26","doi-asserted-by":"publisher","first-page":"1101","DOI":"10.1093\/eurheartj\/eht513","article-title":"Coronary microvascular dysfunction: an update","volume":"35","author":"Crea","year":"2014","journal-title":"Eur Heart J"},{"key":"B27","doi-asserted-by":"publisher","first-page":"2625","DOI":"10.1016\/j.jacc.2018.09.042","article-title":"Coronary microvascular disease pathogenic mechanisms and therapeutic options","volume":"72","author":"Taqueti","year":"2018","journal-title":"J Am Coll Cardiol"},{"key":"B28","doi-asserted-by":"publisher","first-page":"49","DOI":"10.1146\/annurev-physiol-042022-015223","article-title":"The mineralocorticoid receptor in the vasculature: friend or foe?","volume":"86","author":"Ibarrola","year":"2024","journal-title":"Annu Rev Physiol"},{"key":"B29","doi-asserted-by":"publisher","first-page":"8954","DOI":"10.3390\/ijms23168954","article-title":"Mineralocorticoid receptor activation in vascular insulin resistance and dysfunction","volume":"23","author":"Igbekele","year":"2022","journal-title":"Int J Mol Sci"},{"key":"B30","doi-asserted-by":"publisher","first-page":"75","DOI":"10.1007\/s10741-024-10445-3","article-title":"The role of coronary microcirculation in heart failure with preserved ejection fraction: an unceasing odyssey","volume":"30","author":"Dimitriadis","year":"2025","journal-title":"Heart Fail Rev"},{"key":"B31","doi-asserted-by":"publisher","first-page":"6054","DOI":"10.3390\/jcm14176054","article-title":"Coronary microvascular dysfunction: bridging the diagnosis-treatment divide in women with INOCA-A review","volume":"14","author":"Agarwal","year":"2025","journal-title":"J Clin Med"},{"key":"B32","doi-asserted-by":"publisher","first-page":"869","DOI":"10.1007\/s00395-024-01055-z","article-title":"Vasodilator reactive oxygen species ameliorate perturbed myocardial oxygen delivery in exercising swine with multiple comorbidities","volume":"119","author":"van Drie","year":"2024","journal-title":"Basic Res Cardiol"},{"key":"B33","doi-asserted-by":"publisher","first-page":"13294","DOI":"10.3390\/ijms252413294","article-title":"Systemic and cardiac microvascular dysfunction in hypertension","volume":"25","author":"Durante","year":"2024","journal-title":"Int J Mol Sci"},{"key":"B34","doi-asserted-by":"publisher","first-page":"3135","DOI":"10.1111\/bph.15782","article-title":"The role of the mineralocorticoid receptor in immune cells in cardiovascular disease","volume":"179","author":"Van Der Heijden","year":"2022","journal-title":"Br J Pharmacol"},{"key":"B35","doi-asserted-by":"publisher","first-page":"1396","DOI":"10.3390\/antiox12071396","article-title":"Inhibitors of NLRP3 inflammasome in ischemic heart disease: focus on functional and redox aspects","volume":"12","author":"Pagliaro","year":"2023","journal-title":"Antioxidants (Basel)"},{"key":"B36","doi-asserted-by":"publisher","first-page":"1132","DOI":"10.3390\/cells15131132","article-title":"Immunometabolic mechanisms of coronary microvascular dysfunction in coronary artery disease: the role of mitochondrial stress, endothelial senescence, and regulated cell death","volume":"15","author":"Lucki","year":"2026","journal-title":"Cells"},{"key":"B37","doi-asserted-by":"publisher","first-page":"197","DOI":"10.1177\/107424840501000308","article-title":"Beneficial cardiovascular actions of eplerenone in the spontaneously hypertensive rat","volume":"10","author":"Susic","year":"2005","journal-title":"J Cardiovasc Pharmacol Ther"},{"key":"B38","doi-asserted-by":"publisher","first-page":"H1177","DOI":"10.1152\/ajpheart.00866.2009","article-title":"Cardiovascular effects of inhibition of renin-angiotensin-aldosterone system components in hypertensive rats given salt excess","volume":"298","author":"Susic","year":"2010","journal-title":"Am J Physiol Heart Circ Physiol"},{"key":"B39","doi-asserted-by":"publisher","first-page":"2245","DOI":"10.3390\/ijms24032245","article-title":"Cardiovascular disease in obstructive sleep apnea: putative contributions of mineralocorticoid receptors","volume":"24","author":"Badran","year":"2023","journal-title":"Int J Mol Sci"},{"key":"B40","doi-asserted-by":"publisher","first-page":"6","DOI":"10.1007\/s11906-025-01356-1","article-title":"Obstructive sleep apnea and hypertension: is aldosterone blockade the optimal approach to control blood pressure and improve oxygenation?","volume":"28","author":"Ikeda","year":"2026","journal-title":"Curr Hypertens Rep"},{"key":"B41","doi-asserted-by":"publisher","first-page":"zsae296","DOI":"10.1093\/sleep\/zsae296","article-title":"Mineralocorticoid receptor antagonism prevents coronary microvascular dysfunction in intermittent hypoxia independent of blood pressure","volume":"48","author":"Badran","year":"2025","journal-title":"Sleep"},{"key":"B42","doi-asserted-by":"publisher","first-page":"2552","DOI":"10.1210\/jc.2007-0393","article-title":"Beneficial effects of eplerenone versus hydrochlorothiazide on coronary circulatory function in patients with diabetes mellitus","volume":"92","author":"Joffe","year":"2007","journal-title":"J Clin Endocrinol Metab"},{"key":"B43","doi-asserted-by":"publisher","first-page":"236","DOI":"10.2337\/db14-0670","article-title":"Mineralocorticoid receptor blockade improves coronary microvascular function in individuals with type 2 diabetes","volume":"64","author":"Garg","year":"2015","journal-title":"Diabetes"},{"key":"B44","doi-asserted-by":"publisher","first-page":"1166","DOI":"10.1093\/cid\/ciad310","article-title":"Randomized placebo-controlled trial to evaluate effects of eplerenone on myocardial perfusion and function among persons with human immunodeficiency virus (HIV)-results from the MIRACLE HIV study","volume":"77","author":"Srinivasa","year":"2023","journal-title":"Clin Infect Dis"},{"key":"B45","doi-asserted-by":"publisher","first-page":"ehaf784.2158","DOI":"10.1093\/eurheartj\/ehaf784.2158","article-title":"The influence of endothelial dysfunction and the prognosis in patients with myocardial infarction with non-obstructive coronary arteries","volume":"46","author":"Kondo","year":"2025","journal-title":"Eur Heart J"},{"key":"B46","doi-asserted-by":"publisher","first-page":"539","DOI":"10.1016\/j.ejheart.2004.04.013","article-title":"The clinical implications of aldosterone escape in congestive heart failure","volume":"6","author":"Struthers","year":"2004","journal-title":"Eur J Heart Fail"},{"key":"B47","doi-asserted-by":"publisher","first-page":"826","DOI":"10.1016\/j.ahj.2014.01.017","article-title":"Aldosterone inhibition and coronary endothelial function in women without obstructive coronary artery disease: an ancillary study of the national heart, lung, and blood institute-sponsored women's Ischemia syndrome evaluation","volume":"167","author":"Bavry","year":"2014","journal-title":"Am Heart J"}],"container-title":["Frontiers in Cardiovascular Medicine"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fcvm.2026.1855673\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T08:25:23Z","timestamp":1791275123000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fcvm.2026.1855673\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,10,6]]},"references-count":47,"alternative-id":["10.3389\/fcvm.2026.1855673"],"URL":"https:\/\/doi.org\/10.3389\/fcvm.2026.1855673","relation":{},"ISSN":["2297-055X"],"issn-type":[{"value":"2297-055X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,10,6]]},"article-number":"1855673"}}