{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,12]],"date-time":"2026-04-12T03:46:52Z","timestamp":1775965612636,"version":"3.50.1"},"reference-count":40,"publisher":"Oxford University Press (OUP)","issue":"1","license":[{"start":{"date-parts":[[2026,2,3]],"date-time":"2026-02-03T00:00:00Z","timestamp":1770076800000},"content-version":"vor","delay-in-days":1859,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"},{"start":{"date-parts":[[2020,12,24]],"date-time":"2020-12-24T00:00:00Z","timestamp":1608768000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2021,1,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>The pathophysiology of heart failure involves maladaptive angiotensin peptides (APs) and enzymes, including angiotensin 2 (AT2) and angiotensin converting enzyme (ACE), as well as recently described alternative components, such as angiotensin 1-7 (Ang1-7) and angiotensin converting enzyme\u20092 (ACE2). The relative effects of different neurohormonal-targeting drugs on balance of APs in dogs with heart disease are unknown.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Hypothesis\/Objectives<\/jats:title>\n                    <jats:p>Plasma AP concentrations differ in dogs receiving angiotensin converting enzyme inhibitors (ACEIs) vs angiotensin receptor blockers (ARBs) and recombinant human ACE2 (rhACE2) will further increase these differences.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Animals<\/jats:title>\n                    <jats:p>Eight dogs with degenerative mitral valve disease (DMVD).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Prospective open-label trial. Equilibrium concentrations of APs from plasma during PO ACEI treatment and then after 14\u2009days of PO ARB treatment using telmisartan were measured using liquid chromatography-tandem mass spectroscopy before and after in\u2009vitro incubation with rhACE2.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Concentration of Ang1-7 was increased during ARB treatment (Ang1-7: 443\u2009pg\/mL; 95% confidence interval [CI] = 247-794\u2009pg\/mL) vs ACEI (Ang1-7: 182\u2009pg\/mL; 95% CI = 66.2-503\u2009pg\/mL; P = .01). Incubation with rhACE2 decreased traditional APs while increasing beneficial alternative APs, and Ang1-7 was significantly higher in the ARB\u2009+\u2009rhACE2 (880\u2009pg\/mL; 95% CI = 560-1383\u2009pg\/mL) vs ACEI\u2009+\u2009rhACE2 (455\u2009pg\/mL; 95% CI = 188-1104\u2009pg\/mL; P = .03) group. The most favorable theoretical AP profile was achieved in the ARB\u2009+\u2009rhACE2 group.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions and Clinical Importance<\/jats:title>\n                    <jats:p>The AP profile during telmisartan treatment is associated with higher plasma Ang1-7 as compared with during ACEI. This favorable shift is potentiated in vitro by combination of ARB\u2009+\u2009rhACE2. These data support potential AP-targeting strategies and drugs in dogs with DMVD.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/jvim.16025","type":"journal-article","created":{"date-parts":[[2020,12,25]],"date-time":"2020-12-25T04:50:49Z","timestamp":1608871849000},"page":"22-32","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["Effect of angiotensin receptor blockers and angiotensin converting enzyme\u20092 on plasma equilibrium angiotensin peptide concentrations in dogs with heart disease"],"prefix":"10.1093","volume":"35","author":[{"given":"\u00c9va","family":"Larouche-Lebel","sequence":"first","affiliation":[{"name":"School of Veterinary Medicine, University of Pennsylvania Department of Clinical Sciences and Advanced Medicine, , Philadelphia, Pennsylvania,","place":["USA"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kerry A.","family":"Loughran","sequence":"additional","affiliation":[{"name":"School of Veterinary Medicine, University of Pennsylvania Department of Clinical Sciences and Advanced Medicine, , Philadelphia, Pennsylvania,","place":["USA"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Terry","family":"Huh","sequence":"additional","affiliation":[{"name":"School of Veterinary Medicine, University of Pennsylvania Department of Clinical Sciences and Advanced Medicine, , Philadelphia, Pennsylvania,","place":["USA"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5218-9226","authenticated-orcid":false,"given":"Mark A.","family":"Oyama","sequence":"additional","affiliation":[{"name":"School of Veterinary Medicine, University of Pennsylvania Department of Clinical Sciences and Advanced Medicine, , Philadelphia, Pennsylvania,","place":["USA"]},{"name":"Institute for Translational Medicine and Therapeutics, Perelman School of Medicine, University of Pennsylvania , Philadelphia, Pennsylvania,","place":["USA"]}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2021,1,1]]},"reference":[{"key":"2026020922105128400_jvim16025-bib-0001","doi-asserted-by":"crossref","first-page":"109","DOI":"10.1186\/BF03548123","article-title":"Effects of mild mitral valve insufficiency, sodium intake, and place of blood sampling on the renin-angiotensin system in dogs","volume":"37","author":"Pedersen","year":"1996","journal-title":"Acta Vet Scand"},{"key":"2026020922105128400_jvim16025-bib-0002","doi-asserted-by":"crossref","first-page":"328","DOI":"10.1111\/j.1939-1676.1995.tb01092.x","article-title":"Activation of the renin-angiotensin system in dogs with asymptomatic and mildly symptomatic mitral valvular insufficiency","volume":"9","author":"Pedersen","year":"1995","journal-title":"J Vet Intern Med"},{"key":"2026020922105128400_jvim16025-bib-0003","doi-asserted-by":"crossref","first-page":"77","DOI":"10.2460\/ajvr.1997.58.01.77","article-title":"Effects of naturally acquired decompensated mitral valve regurgitation on the renin-angiotensin-aldosterone system and atrial natriuretic peptide concentration in dogs","volume":"58","author":"Haggstrom","year":"1997","journal-title":"Am J Vet Res"},{"key":"2026020922105128400_jvim16025-bib-0004","doi-asserted-by":"crossref","first-page":"C82","DOI":"10.1152\/ajpcell.00287.2006","article-title":"Angiotensin II cell signaling: physiological and pathological effects in the cardiovascular system","volume":"292","author":"Mehta","year":"2007","journal-title":"Am J Physiol Cell Physiol"},{"key":"2026020922105128400_jvim16025-bib-0005","doi-asserted-by":"crossref","first-page":"33238","DOI":"10.1074\/jbc.M002615200","article-title":"A human homolog of angiotensin-converting enzyme. 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