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CHF rats received the vasopeptidase inhibitor (S21402, 100 mg \u00b7 kg<jats:sup>\u2212<\/jats:sup><jats:sup>1<\/jats:sup>\u00b7 d<jats:sup>\u2212<\/jats:sup><jats:sup>1<\/jats:sup>), an ACE inhibitor (captopril, 50 mg \u00b7 kg<jats:sup>\u2212<\/jats:sup><jats:sup>1<\/jats:sup>\u00b7 d<jats:sup>\u2212<\/jats:sup><jats:sup>1<\/jats:sup>), a NEP inhibitor (<jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"genpept\" xlink:href=\"SCH42495\">SCH42495<\/jats:ext-link>, 60 mg \u00b7 kg<jats:sup>\u2212<\/jats:sup><jats:sup>1<\/jats:sup>\u00b7 d<jats:sup>\u2212<\/jats:sup><jats:sup>1<\/jats:sup>), or vehicle for 4 weeks. S21402 alone caused a diuresis and natriuresis (<jats:italic>P<\/jats:italic>&lt;0.01) in CHF. After 4 weeks, blood pressure was lowered by captopril but not other treatments (<jats:italic>P<\/jats:italic>&lt;0.01). Both S21402 and captopril increased plasma renin activity (<jats:italic>P<\/jats:italic>&lt;0.01), all treatment lowered plasma aldosterone (<jats:italic>P<\/jats:italic>&lt;0.05) and plasma natriuretic peptide levels were unchanged. In the kidney, S21402 inhibited NEP and ACE (<jats:italic>P<\/jats:italic>&lt;0.01),<jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"genpept\" xlink:href=\"SCH42495\">SCH42495<\/jats:ext-link>inhibited NEP (<jats:italic>P<\/jats:italic>&lt;0.01), and captopril inhibited ACE (<jats:italic>P<\/jats:italic>&lt;0.01). Heart mass was reduced by all active treatments; captopril reduced left ventricular mass (<jats:italic>P<\/jats:italic>&lt;0.01),<jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"genpept\" xlink:href=\"SCH42495\">SCH42495<\/jats:ext-link>reduced right ventricular mass (<jats:italic>P<\/jats:italic>&lt;0.01), and S21402 decreased left (<jats:italic>P<\/jats:italic>&lt;0.05) and right ventricular mass (<jats:italic>P<\/jats:italic>&lt;0.01), atrial mass (<jats:italic>P<\/jats:italic>&lt;0.05), and lung mass (<jats:italic>P<\/jats:italic>&lt;0.01). In CHF, vasopeptidase inhibition with S21402 produces effects that differ from those of selective NEP or ACE inhibition. S21402 improved sodium and water excretion, reduced pulmonary congestion, and attenuated both right and left ventricular remodeling. These effects, which occurred in the absence of any hypotensive action, suggest that S21402 may offer several advantages over ACE inhibition alone in the treatment of heart failure.<\/jats:p>","DOI":"10.1161\/01.hyp.36.6.1105","type":"journal-article","created":{"date-parts":[[2012,6,12]],"date-time":"2012-06-12T00:25:31Z","timestamp":1339460731000},"page":"1105-1111","update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":21,"title":["Beneficial Renal and Cardiac Effects of Vasopeptidase Inhibition With S21402 in Heart Failure"],"prefix":"10.1161","volume":"36","author":[{"given":"Louise M.","family":"Burrell","sequence":"first","affiliation":[{"name":"From the Department of Medicine, University of Melbourne, Austin and Repatriation Medical Centre, Victoria, Australia."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nicole K.","family":"Farina","sequence":"additional","affiliation":[{"name":"From the Department of Medicine, University of Melbourne, Austin and Repatriation Medical Centre, Victoria, Australia."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Leanne C.","family":"Balding","sequence":"additional","affiliation":[{"name":"From the Department of Medicine, University of Melbourne, Austin and Repatriation Medical Centre, Victoria, Australia."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Colin I.","family":"Johnston","sequence":"additional","affiliation":[{"name":"From the Department of Medicine, University of Melbourne, Austin and Repatriation Medical Centre, Victoria, Australia."}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"276","reference":[{"key":"e_1_3_2_1_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM199209033271001"},{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1161\/circ.88.3.8353861"},{"key":"e_1_3_2_3_2","first-page":"24S","volume":"87","year":"1989","unstructured":"Johnston CI, Hodsman PG, Kohzuki M, Casley DJ, Fabris B, Phillips PA. 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