{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,13]],"date-time":"2026-05-13T04:54:28Z","timestamp":1778648068394,"version":"3.51.4"},"reference-count":15,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2015,3,15]],"date-time":"2015-03-15T00:00:00Z","timestamp":1426377600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"name":"Veterinary Memorial Fund"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Vet Pharm &amp; Therapeutics"],"published-print":{"date-parts":[[2015,10]]},"abstract":"<jats:p>Studies in our laboratory have revealed that furosemide\u2010induced<jats:styled-content style=\"fixed-case\">RAAS<\/jats:styled-content>activation, evaluated via the urine aldosterone\u2010to\u2010creatinine ratio (<jats:styled-content style=\"fixed-case\">UA<\/jats:styled-content>ldo:C), was not attenuated by the coadministration of benazepril, while enalapril successfully suppressed amlodipine\u2010induced urinary aldosterone excretion. This study was designed to evaluate the efficacy of enalapril in suppressing<jats:styled-content style=\"fixed-case\">ACE<\/jats:styled-content>activity and furosemide\u2010induced circulating<jats:styled-content style=\"fixed-case\">RAAS<\/jats:styled-content>activation. Failure to do so would suggest that this failure may be a drug class effect. We hypothesized that enalapril would suppress<jats:styled-content style=\"fixed-case\">ACE<\/jats:styled-content>activity and furosemide\u2010induced circulating<jats:styled-content style=\"fixed-case\">RAAS<\/jats:styled-content>activation. Sixteen healthy hound dogs. The effect of furosemide (2\u00a0mg\/kg<jats:styled-content style=\"fixed-case\">PO<\/jats:styled-content>, q12\u00a0h; Group F) and furosemide plus enalapril (0.5\u00a0mg\/kg<jats:styled-content style=\"fixed-case\">PO<\/jats:styled-content>, q12\u00a0h; Group<jats:styled-content style=\"fixed-case\">FE<\/jats:styled-content>) on circulating<jats:styled-content style=\"fixed-case\">RAAS<\/jats:styled-content>was determined by plasma<jats:styled-content style=\"fixed-case\">ACE<\/jats:styled-content>activity, 4\u20136\u00a0h post\u2010treatment, and urinary A:C on days \u22121, \u22122, 1, 4, and 7. There was a significant increase in the average urine aldosterone\u2010to\u2010creatinine ratio (<jats:styled-content style=\"fixed-case\">UA<\/jats:styled-content>ldo:C) after administration of furosemide (<jats:italic>P<\/jats:italic>\u00a0&lt;\u00a00.05). Enalapril inhibited<jats:styled-content style=\"fixed-case\">ACE<\/jats:styled-content>activity (<jats:italic>P<\/jats:italic>\u00a0&lt;\u00a00.0001) but did not significantly reduce aldosterone excretion. A significant (<jats:italic>P<\/jats:italic>\u00a0&lt;\u00a00.05) increase in the<jats:styled-content style=\"fixed-case\">UA<\/jats:styled-content>ldo:C was maintained for the 7\u00a0days of the study in both groups. Enalapril decreased plasma<jats:styled-content style=\"fixed-case\">ACE<\/jats:styled-content>activity; however, it did not suppress furosemide\u2010induced<jats:styled-content style=\"fixed-case\">RAAS<\/jats:styled-content>activation, as determined by the<jats:styled-content style=\"fixed-case\">UA<\/jats:styled-content>ldo:C. While enalapril blunts<jats:styled-content style=\"fixed-case\">ACE<\/jats:styled-content>activity, the absence of circulating<jats:styled-content style=\"fixed-case\">RAAS<\/jats:styled-content>suppression may be due to angiotensin<jats:styled-content style=\"fixed-case\">II<\/jats:styled-content>reactivation, alternative<jats:styled-content style=\"fixed-case\">RAAS<\/jats:styled-content>pathways, and furosemide overriding concurrent<jats:styled-content style=\"fixed-case\">ACE<\/jats:styled-content>inhibition, all indicating the existence of aldosterone breakthrough (<jats:styled-content style=\"fixed-case\">ABT<\/jats:styled-content>). Along with similar findings with benazepril, it appears that failure to suppress aldosterone suppression with furosemide stimulation may be a drug class effect. The discrepancy between the current data and the documented benefits of enalapril likely reflects the efficacy of this<jats:styled-content style=\"fixed-case\">ACE<\/jats:styled-content>inhibitor in suppressing tissue<jats:styled-content style=\"fixed-case\">RAAS<\/jats:styled-content>, variable population responsiveness to<jats:styled-content style=\"fixed-case\">ACE<\/jats:styled-content>\u2010inhibition, and\/or providing additional survival benefits, possibly through as yet unknown mechanisms.<\/jats:p>","DOI":"10.1111\/jvp.12216","type":"journal-article","created":{"date-parts":[[2015,3,16]],"date-time":"2015-03-16T05:16:39Z","timestamp":1426482999000},"page":"513-517","source":"Crossref","is-referenced-by-count":19,"title":["The effect of enalapril on furosemide\u2010activated renin\u2013angiotensin\u2013aldosterone system in healthy dogs"],"prefix":"10.1111","volume":"38","author":[{"given":"A. C.","family":"Lantis","sequence":"first","affiliation":[{"name":"Department of Small Animal Clinical Sciences Virginia\u2010Maryland Regional College of Veterinary Medicine Blacksburg VA USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"M. K.","family":"Ames","sequence":"additional","affiliation":[{"name":"Department of Small Animal Clinical Sciences Virginia\u2010Maryland Regional College of Veterinary Medicine Blacksburg VA USA"},{"name":"Department of Clinical Sciences College of Veterinary Medicine North Carolina State University Raleigh NC USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"S.","family":"Werre","sequence":"additional","affiliation":[{"name":"Department of Small Animal Clinical Sciences Virginia\u2010Maryland Regional College of Veterinary Medicine Blacksburg VA USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"C. 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