{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T07:28:08Z","timestamp":1790666888257,"version":"4.1.0"},"reference-count":43,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"5","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["Circ: Heart Failure"],"published-print":{"date-parts":[[2012,9]]},"abstract":"<jats:sec>\n            <jats:title>Background\u2014<\/jats:title>\n            <jats:p>TRV120027 is a novel \u03b2-arrestin biased ligand of the angiotensin II type 1 receptor; it antagonizes canonical G-protein\u2013mediated coupling while, in contrast to classical angiotensin II type 1 receptor antagonists, it engages \u03b2-arrestin\u2013mediated signaling. Consequently, TRV120027 inhibits angiotensin II\u2013mediated vasoconstriction while, via \u03b2-arrestin coupling, it increases cardiomyocyte contractility. We hypothesized that TRV120027 would elicit beneficial cardiorenal actions when added to furosemide in experimental heart failure.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Methods and Results\u2014<\/jats:title>\n            <jats:p>\n              Two groups of anesthetized dogs (n=6 each) with tachypacing-induced heart failure were studied. After a baseline clearance, 1 group (F+V) received furosemide (1 mg\/kg per hour) plus saline for 90 minutes, whereas the other (F+T) received the same dose of furosemide plus TRV120027 (0.3 and 1.5 \u00b5g\/kg per minute for 45 minutes each); 2 clearances were done during drug infusion. After a washout, a postinfusion clearance was done; *\n              <jats:italic>P<\/jats:italic>\n              &lt;0.05 between groups. F+V and F+T increased diuresis and natriuresis to a similar extent during drug administration, but urine flow* and urinary sodium excretion* were higher in the postinfusion clearance with F+T. Glomerular filtration rate was preserved in both groups. Renal blood flow increased with F+T but this was not significant versus F+V. Compared with F+V, F+T decreased mean arterial pressure*, systemic* and pulmonary* vascular resistances, and atrial natriuretic peptide*. Pulmonary capillary wedge pressure* decreased to a larger extent with F+T than with F+V.\n            <\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Conclusions\u2014<\/jats:title>\n            <jats:p>When added to furosemide, TRV120027, a novel \u03b2-arrestin biased angiotensin II type 1 receptor ligand, preserved furosemide-mediated natriuresis and diuresis, while reducing cardiac preload and afterload. These results provide support for TRV120027 as a promising novel therapeutic for the treatment of heart failure.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1161\/circheartfailure.112.969220","type":"journal-article","created":{"date-parts":[[2012,8,14]],"date-time":"2012-08-14T01:51:53Z","timestamp":1344909113000},"page":"627-634","update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":124,"title":["TRV120027, a Novel \u03b2-Arrestin Biased Ligand at the Angiotensin II Type I Receptor, Unloads the Heart and Maintains Renal Function When Added to Furosemide in Experimental Heart Failure"],"prefix":"10.1161","volume":"5","author":[{"given":"Guido","family":"Boerrigter","sequence":"first","affiliation":[{"name":"From the Cardiorenal Research Laboratory, Mayo Clinic and Foundation, Rochester, MN (G.B., J.C.B.); and Trevena Inc, King of Prussia, PA (D.G.S., J.D.V., M.W.L.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David G.","family":"Soergel","sequence":"additional","affiliation":[{"name":"From the Cardiorenal Research Laboratory, Mayo Clinic and Foundation, Rochester, MN (G.B., J.C.B.); and Trevena Inc, King of Prussia, PA (D.G.S., J.D.V., M.W.L.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jonathan D.","family":"Violin","sequence":"additional","affiliation":[{"name":"From the Cardiorenal Research Laboratory, Mayo Clinic and Foundation, Rochester, MN (G.B., J.C.B.); and Trevena Inc, King of Prussia, PA (D.G.S., J.D.V., M.W.L.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael W.","family":"Lark","sequence":"additional","affiliation":[{"name":"From the Cardiorenal Research Laboratory, Mayo Clinic and Foundation, Rochester, MN (G.B., J.C.B.); and Trevena Inc, King of Prussia, PA (D.G.S., J.D.V., M.W.L.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"suffix":"Jr","given":"John C.","family":"Burnett","sequence":"additional","affiliation":[{"name":"From the Cardiorenal Research Laboratory, Mayo Clinic and Foundation, Rochester, MN (G.B., J.C.B.); and Trevena Inc, King of Prussia, PA (D.G.S., J.D.V., M.W.L.)."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1161\/cir.0b013e3182009701"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1005419"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1161\/01.CIR.102.2.203"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0735-1097(99)00608-7"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.1161\/circulationaha.105.580506"},{"key":"e_1_3_2_7_2","doi-asserted-by":"publisher","DOI":"10.1054\/jcaf.2002.125289"},{"key":"e_1_3_2_8_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jacc.2003.07.031"},{"key":"e_1_3_2_9_2","doi-asserted-by":"publisher","DOI":"10.1093\/eurjhf\/hfp108"},{"key":"e_1_3_2_10_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrd3024"},{"key":"e_1_3_2_11_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.84.24.8879"},{"key":"e_1_3_2_12_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.2163110"},{"key":"e_1_3_2_13_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.283.5402.655"},{"key":"e_1_3_2_14_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.041604898"},{"key":"e_1_3_2_15_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M207294200"},{"key":"e_1_3_2_16_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.290.5496.1574"},{"key":"e_1_3_2_17_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI25330"},{"key":"e_1_3_2_18_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.tips.2007.06.006"},{"key":"e_1_3_2_19_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.molmed.2010.11.004"},{"key":"e_1_3_2_20_2","doi-asserted-by":"publisher","DOI":"10.1126\/scisignal.2000769"},{"key":"e_1_3_2_21_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1834556100"},{"key":"e_1_3_2_22_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M405878200"},{"key":"e_1_3_2_23_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0607583103"},{"key":"e_1_3_2_24_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1742-7843.2007.00063.x"},{"key":"e_1_3_2_25_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0912852107"},{"key":"e_1_3_2_26_2","doi-asserted-by":"publisher","DOI":"10.1124\/mol.111.072801"},{"key":"e_1_3_2_27_2","doi-asserted-by":"publisher","DOI":"10.1126\/scisignal.2002522"},{"key":"e_1_3_2_28_2","doi-asserted-by":"publisher","DOI":"10.1124\/jpet.110.173005"},{"key":"e_1_3_2_29_2","doi-asserted-by":"publisher","DOI":"10.1161\/circheartfailure.111.962571"},{"key":"e_1_3_2_30_2","doi-asserted-by":"publisher","DOI":"10.1161\/01.HYP.37.4.1089"},{"key":"e_1_3_2_31_2","doi-asserted-by":"publisher","DOI":"10.1161\/01.CIR.100.24.2443"},{"key":"e_1_3_2_32_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(09)60622-X"},{"key":"e_1_3_2_33_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1100171"},{"key":"e_1_3_2_34_2","doi-asserted-by":"publisher","DOI":"10.1093\/eurjhf\/hfr060"},{"key":"e_1_3_2_35_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ccm.2006.12.001"},{"key":"e_1_3_2_36_2","doi-asserted-by":"publisher","DOI":"10.1139\/y84-065"},{"key":"e_1_3_2_37_2","doi-asserted-by":"publisher","DOI":"10.1152\/physrev.2000.80.1.277"},{"issue":"1","key":"e_1_3_2_38_2","first-page":"H250","article-title":"Angiotensin II receptor antagonism in ovine heart failure: acute hemodynamic, hormonal, and renal effects.","volume":"263","author":"Fitzpatrick MA","year":"1992","unstructured":"Fitzpatrick MA, Rademaker MT, Charles CJ, Yandle TG, Espiner EA, Ikram H. 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