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Female C57BL6J mice were fed a WD with or without Sp (1 mg\u00b7kg\n                    <jats:sup>\u22121<\/jats:sup>\n                    \u00b7day\n                    <jats:sup>\u22121<\/jats:sup>\n                    ). After 4 mo on the WD, mice exhibited increased body weight and visceral fat, but similar blood pressures, compared with control diet-fed mice. Sp prevented the development of WD-induced DD, as indicated by decreased isovolumic relaxation time and an improvement in myocardial performance (&lt;Tei index) and septal annular velocity (&lt; E\u2032-to- A\u2032 ratio), as assessed by echocardiography, as well as decreased diastolic relaxation time\/increased diastolic initial filling rate, as assessed by MRI. The relationship between passive sarcomere length of cardiac myocytes and ventricular pressure was monitored using di-8-ANEPPS staining of the t-tubule network in hearts ex vivo. Sp administration led to longer sarcomere lengths at each pressure indicative of improved ventricular compliance in WD-fed mice. Sp also prevented left ventricular hypertrophy, interstitial fibrosis, and oxidative stress. Sp prevented the WD-induced increased expression of myocardial proinflammatory M1 macrophage markers monocyte chemoattractant protein-1 and CD11c and increased the expression of the anti-inflammatory M2 macrophage marker CD206. These findings demonstrate that WD-induced DD is associated with increased oxidant stress, fibrosis, and immune dysregulation. Mineralocorticoid receptor antagonism enhanced M2 macrophage polarization and ameliorated oxidant stress and fibrosis. This work supports a novel blood pressure-independent effect of MR antagonism as a strategy to prevent diet-induced DD in women.\n                  <\/jats:p>","DOI":"10.1152\/ajpheart.00898.2014","type":"journal-article","created":{"date-parts":[[2015,3,6]],"date-time":"2015-03-06T22:42:41Z","timestamp":1425681761000},"page":"H1126-H1135","source":"Crossref","is-referenced-by-count":74,"title":["Mineralocorticoid receptor blockade prevents Western diet-induced diastolic dysfunction in female mice"],"prefix":"10.1152","volume":"308","author":[{"given":"Brian","family":"Bostick","sequence":"first","affiliation":[{"name":"Division of Cardiovascular Medicine, Department of Medicine, University of Missouri, Columbia, Missouri;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Javad","family":"Habibi","sequence":"additional","affiliation":[{"name":"Division of Endocrinology, Diabetes and Metabolism, University of Missouri, Columbia, Missouri;"},{"name":"Research Service, Harry S. 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