{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,14]],"date-time":"2026-03-14T03:31:12Z","timestamp":1773459072589,"version":"3.50.1"},"reference-count":23,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"17","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["Circulation"],"published-print":{"date-parts":[[1998,10,27]]},"abstract":"<jats:p><jats:italic>Background<\/jats:italic>\u2014The regulation and interaction of ACE and the angiotensin II (Ang II) type I (AT<jats:sub>1<\/jats:sub>) receptor in the failing human heart are not understood.<\/jats:p><jats:p><jats:italic>Methods and Results<\/jats:italic>\u2014Radioligand binding with<jats:sup>3<\/jats:sup>H-ramiprilat was used to measure ACE protein in membrane preparations of hearts obtained from 36 subjects with idiopathic dilated cardiomyopathy (IDC), 8 subjects with primary pulmonary hypertension (PPH), and 32 organ donors with normal cardiac function (NF hearts).<jats:sup>125<\/jats:sup>I-Ang II formation was measured in a subset of hearts. Saralasin (<jats:sup>125<\/jats:sup>I-{Sar<jats:sup>1<\/jats:sup>,Ile<jats:sup>8<\/jats:sup>}-Ang II) was used to measure total Ang II receptor density. AT<jats:sub>1<\/jats:sub>and AT<jats:sub>2<\/jats:sub>receptor binding were determined with the AT<jats:sub>1<\/jats:sub>receptor antagonist losartan. Maximal ACE binding (<jats:italic>B<\/jats:italic><jats:sub>max<\/jats:sub>) was 578\u00b147 fmol\/mg in IDC left ventricle (LV), 713\u00b197 fmol\/mg in PPH LV, and 325\u00b127 fmol\/mg in NF LV (<jats:italic>P<\/jats:italic>&lt;0.001, IDC or PPH versus NF). In IDC, PPH, and NF right ventricles (RV), ACE<jats:italic>B<\/jats:italic><jats:sub>max<\/jats:sub>was 737\u00b178, 638\u00b1137, and 422\u00b149 fmol\/mg, respectively (<jats:italic>P<\/jats:italic>=0.02, IDC versus NF;<jats:italic>P<\/jats:italic>=0.08, PPH versus NF).<jats:sup>125<\/jats:sup>I-Ang II formation correlated with ACE binding sites (<jats:italic>r<\/jats:italic>=0.60,<jats:italic>P<\/jats:italic>=0.00005). There was selective downregulation of the AT<jats:sub>1<\/jats:sub>receptor subtype in failing PPH ventricles: 6.41\u00b11.23 fmol\/mg in PPH LV, 2.37\u00b10.50 fmol\/mg in PPH RV, 5.38\u00b10.53 fmol\/mg in NF LV, and 7.30\u00b11.10 fmol\/mg in NF RV (<jats:italic>P<\/jats:italic>=0.01, PPH RV versus PPH LV;<jats:italic>P<\/jats:italic>=0.0006, PPH RV versus NF RV).<\/jats:p><jats:p><jats:italic>Conclusions<\/jats:italic>\u2014ACE binding sites are increased in both failing IDC and nonfailing PPH ventricles. In PPH hearts, the AT<jats:sub>1<\/jats:sub>receptor is downregulated only in the failing RV.<\/jats:p>","DOI":"10.1161\/01.cir.98.17.1735","type":"journal-article","created":{"date-parts":[[2012,6,12]],"date-time":"2012-06-12T00:41:02Z","timestamp":1339461662000},"page":"1735-1741","update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":38,"title":["Differential Regulation of Cardiac Angiotensin Converting Enzyme Binding Sites and AT<sub>1<\/sub>Receptor Density in the Failing Human Heart"],"prefix":"10.1161","volume":"98","author":[{"given":"Lawrence S.","family":"Zisman","sequence":"first","affiliation":[{"name":"From the Department of Medicine, Division of Cardiology, University of Colorado Health Sciences Center, Denver."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Koji","family":"Asano","sequence":"additional","affiliation":[{"name":"From the Department of Medicine, Division of Cardiology, University of Colorado Health Sciences Center, Denver."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Darrin L.","family":"Dutcher","sequence":"additional","affiliation":[{"name":"From the Department of Medicine, Division of Cardiology, University of Colorado Health Sciences Center, Denver."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anthony","family":"Ferdensi","sequence":"additional","affiliation":[{"name":"From the Department of Medicine, Division of Cardiology, University of Colorado Health Sciences Center, Denver."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alastair D.","family":"Robertson","sequence":"additional","affiliation":[{"name":"From the Department of Medicine, Division of Cardiology, University of Colorado Health Sciences Center, Denver."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Matthew","family":"Jenkin","sequence":"additional","affiliation":[{"name":"From the Department of Medicine, Division of Cardiology, University of Colorado Health Sciences Center, Denver."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Erik W.","family":"Bush","sequence":"additional","affiliation":[{"name":"From the Department of Medicine, Division of Cardiology, University of Colorado Health Sciences Center, Denver."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Teresa","family":"Bohlmeyer","sequence":"additional","affiliation":[{"name":"From the Department of Medicine, Division of Cardiology, University of Colorado Health Sciences Center, Denver."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"M. Benjamin","family":"Perryman","sequence":"additional","affiliation":[{"name":"From the Department of Medicine, Division of Cardiology, University of Colorado Health Sciences Center, Denver."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michael R.","family":"Bristow","sequence":"additional","affiliation":[{"name":"From the Department of Medicine, Division of Cardiology, University of Colorado Health Sciences Center, Denver."}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"276","reference":[{"key":"e_1_3_2_1_2","doi-asserted-by":"publisher","DOI":"10.1136\/hrt.52.5.530"},{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1093\/eurheartj\/14.2.273"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM199108013250501"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM199108013250502"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1161\/circ.89.1.8281685"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.1161\/circ.88.2.8393389"},{"key":"e_1_3_2_7_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.92.23.10663"},{"key":"e_1_3_2_8_2","doi-asserted-by":"publisher","DOI":"10.1161\/circ.95.5.1193"},{"key":"e_1_3_2_9_2","doi-asserted-by":"publisher","DOI":"10.1161\/circ.95.5.1201"},{"key":"e_1_3_2_10_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI117322"},{"key":"e_1_3_2_11_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI115659"},{"key":"e_1_3_2_12_2","doi-asserted-by":"publisher","DOI":"10.1161\/01.RES.59.3.297"},{"key":"e_1_3_2_13_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1476-5381.1992.tb14530.x"},{"key":"e_1_3_2_14_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0021-9258(18)31543-6"},{"key":"e_1_3_2_15_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI117820"},{"key":"e_1_3_2_16_2","doi-asserted-by":"publisher","DOI":"10.1161\/circ.96.1.220"},{"key":"e_1_3_2_17_2","doi-asserted-by":"publisher","DOI":"10.1161\/res.66.4.2156635"},{"key":"e_1_3_2_18_2","doi-asserted-by":"publisher","DOI":"10.1161\/res.80.2.219"},{"key":"e_1_3_2_19_2","doi-asserted-by":"crossref","first-page":"601","DOI":"10.1016\/S0026-895X(25)10511-7","volume":"48","year":"1995","unstructured":"Lassegue B, Alexander RW, Nickenig G, Clark M, Murphy TJ, Griendling KK. Angiotensin II down-regulates the vascular smooth muscle AT1 receptor by transcriptional and post-transcriptional mechanisms: evidence for homologous and heterologous regulation. 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