{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,19]],"date-time":"2026-02-19T00:38:32Z","timestamp":1771461512919,"version":"3.50.1"},"reference-count":37,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"4","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["Hypertension"],"published-print":{"date-parts":[[2000,10]]},"abstract":"<jats:p><jats:italic>Abstract<\/jats:italic>\u2014Omapatrilat is a member of the new drug class of vasopeptidase inhibitors that may offer benefit in the treatment of heart failure (HF) through simultaneous inhibition of angiotensin-converting enzyme and neutral endopeptidase. We examined the effects of omapatrilat in a placebo-controlled crossover study using a pacing model of HF. Seven sheep were paced sequentially at 180 bpm (mild HF) and then 225 bpm (severe HF) for 7 days each. Omapatrilat (0.005 mg\/kg) or vehicle was administered by intravenous bolus on days 4 to 7 of each paced period. Omapatrilat lowered mean arterial and left atrial pressure and increased cardiac output acutely and chronically in both mild and severe HF (<jats:italic>P<\/jats:italic>&lt;0.01 for all). Plasma atrial and brain natriuretic peptide and cGMP levels were stable acutely (<jats:italic>P<\/jats:italic>=NS), while brain natriuretic peptide increased after repeated dosing in severe HF (<jats:italic>P<\/jats:italic>&lt;0.05). Plasma renin activity rose, whereas angiotensin II and aldosterone levels fell after acute and repeated dosing in both states (<jats:italic>P<\/jats:italic>&lt;0.01 for all). Omapatrilat increased urinary sodium excretion by day 7 in both mild and severe HF (<jats:italic>P<\/jats:italic>&lt;0.05). Effective renal plasma flow and glomerular filtration rate increased or were stable after omapatrilat in mild and severe HF after both acute and repeated dosing. Omapatrilat exhibited pronounced acute and sustained beneficial hemodynamic and renal effects in both mild and severe heart failure.<\/jats:p>","DOI":"10.1161\/01.hyp.36.4.523","type":"journal-article","created":{"date-parts":[[2012,6,12]],"date-time":"2012-06-12T00:25:31Z","timestamp":1339460731000},"page":"523-530","update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":30,"title":["Beneficial Renal and Hemodynamic Effects of Omapatrilat in Mild and Severe Heart Failure"],"prefix":"10.1161","volume":"36","author":[{"given":"Richard W.","family":"Troughton","sequence":"first","affiliation":[{"name":"From the Christchurch Cardioendocrine Research Group, Christchurch Hospital and Christchurch School of Medicine, Christchurch, New Zealand."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Miriam T.","family":"Rademaker","sequence":"additional","affiliation":[{"name":"From the Christchurch Cardioendocrine Research Group, Christchurch Hospital and Christchurch School of Medicine, Christchurch, New Zealand."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"James D.","family":"Powell","sequence":"additional","affiliation":[{"name":"From the Christchurch Cardioendocrine Research Group, Christchurch Hospital and Christchurch School of Medicine, Christchurch, New Zealand."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Timothy G.","family":"Yandle","sequence":"additional","affiliation":[{"name":"From the Christchurch Cardioendocrine Research Group, Christchurch Hospital and Christchurch School of Medicine, Christchurch, New Zealand."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Eric A.","family":"Espiner","sequence":"additional","affiliation":[{"name":"From the Christchurch Cardioendocrine Research Group, Christchurch Hospital and Christchurch School of Medicine, Christchurch, New Zealand."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Christopher M.","family":"Frampton","sequence":"additional","affiliation":[{"name":"From the Christchurch Cardioendocrine Research Group, Christchurch Hospital and Christchurch School of Medicine, Christchurch, New Zealand."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"M. Gary","family":"Nicholls","sequence":"additional","affiliation":[{"name":"From the Christchurch Cardioendocrine Research Group, Christchurch Hospital and Christchurch School of Medicine, Christchurch, New Zealand."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"A. Mark","family":"Richards","sequence":"additional","affiliation":[{"name":"From the Christchurch Cardioendocrine Research Group, Christchurch Hospital and Christchurch School of Medicine, Christchurch, New Zealand."}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"276","reference":[{"key":"e_1_3_2_1_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM200001203420301"},{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1161\/circ.82.5.2225374"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1053\/euhj.1998.1093"},{"key":"e_1_3_2_4_2","unstructured":"Francis GS McDonald KM Cohn JN. Neurohumoral activation in preclinical heart failure: remodeling and the potential for intervention. Circulation. 1993;87(suppl IV):IV-90\u2013IV-96."},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1159\/000006808"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM198706043162301"},{"key":"e_1_3_2_7_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM199108013250501"},{"key":"e_1_3_2_8_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(98)11181-9"},{"key":"e_1_3_2_9_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM199909023411001"},{"key":"e_1_3_2_10_2","first-page":"S37","volume":"17","year":"1999","unstructured":"Burnett JC Jr. Vasopeptidase inhibition: a new concept in blood pressure management. J Hypertens Suppl. 1999;17:S37\u2013S43.","journal-title":"Suppl"},{"key":"e_1_3_2_11_2","doi-asserted-by":"publisher","DOI":"10.1016\/0014-5793(88)80375-2"},{"key":"e_1_3_2_12_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0006-291X(05)81194-5"},{"key":"e_1_3_2_13_2","doi-asserted-by":"publisher","DOI":"10.1096\/fasebj.3.2.2521610"},{"key":"e_1_3_2_14_2","doi-asserted-by":"crossref","first-page":"745","DOI":"10.1016\/S0022-3565(25)12124-1","volume":"275","year":"1995","unstructured":"Trippodo NC, Robl JA, Asaad MM, Bird JE, Panchal BC, Schaeffer TR, Fox M, Giancarli MR, Cheung HS. Cardiovascular effects of the novel dual inhibitor of neutral endopeptidase and angiotensin-converting enzyme BMS-182657 in experimental hypertension and heart failure. J Pharmacol Exp Ther. 1995;275:745\u2013752.","journal-title":"J Pharmacol Exp Ther"},{"key":"e_1_3_2_15_2","doi-asserted-by":"publisher","DOI":"10.1097\/00005344-199801000-00017"},{"key":"e_1_3_2_16_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0009-9236(99)70140-2"},{"key":"e_1_3_2_17_2","doi-asserted-by":"publisher","DOI":"10.1097\/00005344-199812000-00006"},{"key":"e_1_3_2_18_2","first-page":"I","volume":"100","year":"1999","unstructured":"Chen Horng H, Lainchbury JG, Harty GJ, Burnett JC Jr. Acute NEP\/ACE inhibition by omapatrilat is superior to ACE inhibition alone in mediating favorable cardiorenal and humoral actions in early left ventricular dysfunction. Circulation. 1999;100:I-298. Abstract.","journal-title":"Circulation"},{"key":"e_1_3_2_19_2","doi-asserted-by":"publisher","DOI":"10.1097\/00005344-199010000-00015"},{"key":"e_1_3_2_20_2","doi-asserted-by":"publisher","DOI":"10.1016\/0002-9149(92)91194-9"},{"key":"e_1_3_2_21_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0895-7061(97)00404-4"},{"key":"e_1_3_2_22_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0735-1097(00)00741-5"},{"key":"e_1_3_2_23_2","first-page":"I","volume":"100","year":"1999","unstructured":"Lainchbury JG, Burnett JC Jr. The cardiac hormone atrial natriuretic peptide mediates hemodynamic actions of dual enzyme inhibition in early left ventricular dysfunction. Circulation. 1999;100:I-438. Abstract.","journal-title":"Circulation"},{"key":"e_1_3_2_24_2","first-page":"I","volume":"100","year":"1999","unstructured":"Rouleau JL, Pfeffer MA, Stewart DJ, Kenut EK, Porter CB, Parker JO, Smith LK, Proulx G, Qian C, Block AJ. Vasopeptidase inhibitor or angiotensin converting enzyme inhibitor in heart failure? Results of the IMPRESS trial. Circulation. 1999;100:I-782. Abstract.","journal-title":". Circulation"},{"key":"e_1_3_2_25_2","doi-asserted-by":"publisher","DOI":"10.1152\/ajpheart.1989.256.4.H1052"},{"key":"e_1_3_2_26_2","doi-asserted-by":"publisher","DOI":"10.1152\/ajpheart.1996.270.2.H594"},{"key":"e_1_3_2_27_2","first-page":"H1625","volume":"258","year":"1990","unstructured":"Fitzpatrick MA, Rademaker MT, Frampton CM, Charles CJ, Yandle TG, Espiner EA, Ikram H. Hemodynamic and hormonal effects of renin inhibition in ovine heart failure. Am J Physiol. 1990;258:H1625\u2013H1631.","journal-title":"Am J Physiol"},{"key":"e_1_3_2_28_2","unstructured":"Wilkinson L Evanston I. Systat: The System for Statistics. Chicago Illinois: Systat Inc; 1990."},{"key":"e_1_3_2_29_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0002-8703(99)70079-7"},{"key":"e_1_3_2_30_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1440-1681.1989.tb01579.x"},{"key":"e_1_3_2_31_2","doi-asserted-by":"publisher","DOI":"10.1161\/circ.100.24.2443"},{"key":"e_1_3_2_32_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0889-8529(18)30028-8"},{"key":"e_1_3_2_33_2","doi-asserted-by":"publisher","DOI":"10.1161\/hyp.30.2.168"},{"key":"e_1_3_2_34_2","doi-asserted-by":"publisher","DOI":"10.1159\/000177059"},{"key":"e_1_3_2_35_2","doi-asserted-by":"publisher","DOI":"10.1097\/00004872-199917030-00017"},{"key":"e_1_3_2_36_2","doi-asserted-by":"publisher","DOI":"10.1038\/324473a0"},{"key":"e_1_3_2_37_2","doi-asserted-by":"publisher","DOI":"10.1161\/res.59.3.2945668"}],"container-title":["Hypertension"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.ahajournals.org\/doi\/full\/10.1161\/01.HYP.36.4.523","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,3,30]],"date-time":"2025-03-30T19:39:49Z","timestamp":1743363589000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.ahajournals.org\/doi\/10.1161\/01.HYP.36.4.523"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2000,10]]},"references-count":37,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2000,10]]}},"alternative-id":["10.1161\/01.HYP.36.4.523"],"URL":"https:\/\/doi.org\/10.1161\/01.hyp.36.4.523","relation":{},"ISSN":["0194-911X","1524-4563"],"issn-type":[{"value":"0194-911X","type":"print"},{"value":"1524-4563","type":"electronic"}],"subject":[],"published":{"date-parts":[[2000,10]]},"assertion":[{"value":"2000-02-16","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2000-04-24","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2000-10-01","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}