{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,4]],"date-time":"2026-10-04T05:38:41Z","timestamp":1791092321769,"version":"4.1.0"},"reference-count":34,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"2","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["Hypertension"],"published-print":{"date-parts":[[2002,8]]},"abstract":"<jats:p>\n            Elevated aldosterone levels induce a spironolactone-inhibitable decrease in cardiac sarcolemmal Na\n            <jats:sup>+<\/jats:sup>\n            -K\n            <jats:sup>+<\/jats:sup>\n            pump function. Because pump inhibition has been shown to contribute to myocyte hypertrophy, restoration of Na\n            <jats:sup>+<\/jats:sup>\n            -K\n            <jats:sup>+<\/jats:sup>\n            pump function may represent a possible mechanism for the cardioprotective action of mineralocorticoid receptor (MR) blockade. The present study examines whether treatment with the angiotensin type 1 receptor antagonist losartan, with either spironolactone or eplerenone, has additive effects on sarcolemmal Na\n            <jats:sup>+<\/jats:sup>\n            -K\n            <jats:sup>+<\/jats:sup>\n            pump activity in hyperaldosteronemia. New Zealand White rabbits were divided into 7 different groups: controls, aldosterone alone, aldosterone plus spironolactone, aldosterone plus eplerenone, aldosterone plus losartan, aldosterone plus losartan and spironolactone, and aldosterone plus losartan and eplerenone. After 7 days, myocytes were isolated by enzymatic digestion. Electrogenic Na\n            <jats:sup>+<\/jats:sup>\n            -K\n            <jats:sup>+<\/jats:sup>\n            pump current (I\n            <jats:sub>p<\/jats:sub>\n            ), arising from the 3:2 Na\n            <jats:sup>+<\/jats:sup>\n            :K\n            <jats:sup>+<\/jats:sup>\n            exchange ratio, was measured by the whole-cell patch clamp technique. Elevated aldosterone levels lowered I\n            <jats:sub>p<\/jats:sub>\n            ; treatment with losartan reversed aldosterone-induced reduced pump function, as did MR blockade. Coadministration of spironolactone or eplerenone with losartan enhanced the losartan effect on pump function to a level similar to that measured in rabbits given losartan alone in the absence of hyperaldosteronemia. In conclusion, hyperaldosteronemia induces a decrease in I\n            <jats:sub>p<\/jats:sub>\n            at near physiological levels of intracellular Na\n            <jats:sup>+<\/jats:sup>\n            concentration. Treatment with losartan reverses this aldosterone-induced decrease in pump function, and coadministration with MR antagonists produces an additive effect on pump function, consistent with a beneficial effect of MR blockade in patients with hypertension and congestive heart failure treated with angiotensin type 1 receptor antagonists.\n          <\/jats:p>","DOI":"10.1161\/01.hyp.0000025904.23047.27","type":"journal-article","created":{"date-parts":[[2002,10,1]],"date-time":"2002-10-01T21:44:29Z","timestamp":1033508669000},"page":"124-129","update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":16,"title":["Mineralocorticoid and Angiotensin Receptor Antagonism During Hyperaldosteronemia"],"prefix":"10.1161","volume":"40","author":[{"given":"Anastasia S.","family":"Mihailidou","sequence":"first","affiliation":[{"name":"From the Department of Cardiology, Royal North Shore Hospital (A.S.M., M.M., M.R.), Sydney, Australia; The University of Sydney (A.S.M., M.M.), Sydney, Australia; and Baker Medical Research Institute (J.W.F.), Melbourne, Australia."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mahidi","family":"Mardini","sequence":"additional","affiliation":[{"name":"From the Department of Cardiology, Royal North Shore Hospital (A.S.M., M.M., M.R.), Sydney, Australia; The University of Sydney (A.S.M., M.M.), Sydney, Australia; and Baker Medical Research Institute (J.W.F.), Melbourne, Australia."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John W.","family":"Funder","sequence":"additional","affiliation":[{"name":"From the Department of Cardiology, Royal North Shore Hospital (A.S.M., M.M., M.R.), Sydney, Australia; The University of Sydney (A.S.M., M.M.), Sydney, Australia; and Baker Medical Research Institute (J.W.F.), Melbourne, Australia."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthew","family":"Raison","sequence":"additional","affiliation":[{"name":"From the Department of Cardiology, Royal North Shore Hospital (A.S.M., M.M., M.R.), Sydney, Australia; The University of Sydney (A.S.M., M.M.), Sydney, Australia; and Baker Medical Research Institute (J.W.F.), Melbourne, Australia."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","reference":[{"key":"e_1_3_2_1_2","doi-asserted-by":"publisher","DOI":"10.1161\/circ.82.5.2225374"},{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1007\/BF00877755"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1071-9164(96)80009-1"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1161\/circ.100.10.1056"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM199909023411001"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.1291\/hypres.22.17"},{"key":"e_1_3_2_7_2","doi-asserted-by":"publisher","DOI":"10.1161\/res.86.1.37"},{"key":"e_1_3_2_8_2","first-page":"15249","volume":"24","year":"1998","unstructured":"Komentiani P, Li J, Gnudi L, Kahn BB, Askari A, Xie Z. 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