{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,4]],"date-time":"2026-10-04T05:38:42Z","timestamp":1791092322786,"version":"4.1.0"},"reference-count":48,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2009,1,29]],"date-time":"2009-01-29T00:00:00Z","timestamp":1233187200000},"content-version":"vor","delay-in-days":1308,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["bpspubs.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["British J Pharmacology"],"published-print":{"date-parts":[[2005,7]]},"abstract":"<jats:p>\n<jats:list list-type=\"explicit-label\">\n<jats:list-item><jats:p>Mineralocorticoid receptor (MR) antagonism with spironolactone reduces mortality in heart failure on top of ACE inhibition. To investigate the underlying mechanism, we compared the actions of both aldosterone and spironolactone to those of angiotensin (Ang) II in the rat heart.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>Hearts of male Wistar rats were perfused according to Langendorff. Ang II and aldosterone increased left ventricular pressure (LVP) by maximally 11\u00b14 and 9\u00b12%, and decreased coronary flow (CF) by maximally 36\u00b17 and 20\u00b14%, respectively. Spironolactone did not significantly affect LVP or CF.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>In hearts that were exposed to a 45\u2010min coronary artery occlusion and 3\u2003h of reperfusion, a 15\u2010min exposure to spironolactone prior to occlusion reduced infarct size (% of risk area) from 68\u00b12 to 45\u00b13%, similar to the reduction (34\u00b12%) observed following \u2018preconditioning\u2019 (15\u2003min occlusion followed by 10\u2003min reperfusion) prior to the 45\u2010min occlusion. Aldosterone exposure did not affect infarct size (71\u00b15%).<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>In cardiomyocytes, aldosterone decreased [<jats:sup>3<\/jats:sup>H]thymidine incorporation maximally by 73\u00b13%, whereas in cardiac fibroblasts it decreased [<jats:sup>3<\/jats:sup>H]proline incorporation by 33\u00b17%. Spironolactone inhibited both effects. Ang II increased DNA and collagen synthesis, and these effects were reversed by aldosterone.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>In conclusion, aldosterone induces positive inotropic and vasoconstrictor effects in a nongenomic manner, and these effects are comparable to those of Ang II. Aldosterone reduces DNA and collagen synthesis <jats:italic>via<\/jats:italic> MR activation, and counteracts the Ang II\u2010induced increases in these parameters. MR blockade reduces infarct size and increases LVP recovery following coronary artery occlusion. The MR\u2010related phenomena may underlie, at least in part, the beneficial actions of spironolactone in heart failure.<\/jats:p><\/jats:list-item>\n<\/jats:list>\n<\/jats:p><jats:p><jats:italic>British Journal of Pharmacology<\/jats:italic> (2005) <jats:bold>145<\/jats:bold>, 664\u2013671. doi:<jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"doi\" xlink:href=\"10.1038\/sj.bjp.0706220\">10.1038\/sj.bjp.0706220<\/jats:ext-link><\/jats:p>","DOI":"10.1038\/sj.bjp.0706220","type":"journal-article","created":{"date-parts":[[2005,4,18]],"date-time":"2005-04-18T10:24:11Z","timestamp":1113819851000},"page":"664-671","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":41,"title":["Genomic and nongenomic effects of aldosterone in the rat heart: why is spironolactone cardioprotective?"],"prefix":"10.1111","volume":"145","author":[{"given":"Wenxia","family":"Chai","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ingrid M","family":"Garrelds","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Udayasankar","family":"Arulmani","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Regien G","family":"Schoemaker","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jos M J","family":"Lamers","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A H Jan","family":"Danser","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2009,1,29]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1161\/01.CIR.0000151516.84238.37"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1161\/01.HYP.0000025879.29822.24"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.102673599"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1006\/jmcc.1994.1098"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1161\/01.CIR.0000048189.58449.F7"},{"key":"e_1_2_7_7_1","doi-asserted-by":"crossref","first-page":"487","DOI":"10.1093\/ajh\/6.6.487","article-title":"Myocardial fibrosis in the rat with mineralocorticoid excess. 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