{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T03:50:25Z","timestamp":1791345025023,"version":"4.3.1"},"reference-count":26,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"4","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["Circulation Research"],"published-print":{"date-parts":[[1996,4]]},"abstract":"<jats:p>\n            <jats:italic>Abstract<\/jats:italic>\n            To study the physiological effect of the overexpression of myocardial G\n            <jats:sub>s\u03b1<\/jats:sub>\n            (protein levels increased by approximately threefold in transgenic mice), we examined the responsiveness to sympathomimetic amines by echocardiography (9 MHz) in five transgenic mice and five control mice (both 10.3\u00b10.2 months old). Myocardial contractility in transgenic mice, as assessed by left ventricular (LV) fractional shortening (LVFS) and LV ejection fraction (LVEF), was not different from that of control mice at baseline (LVFS, 40\u00b13% versus 36\u00b12%; LVEF, 78\u00b13% versus 74\u00b13%). LVFS and LVEF values in transgenic mice during isoproterenol (ISO, 0.02 \u03bcg\/kg per minute) infusion were higher than the values in control mice (LVFS, 68\u00b14% versus 48\u00b13%; LVEF, 96\u00b11% versus 86\u00b13%;\n            <jats:italic>P<\/jats:italic>\n            &lt;.05). Norepinephrine (NE, 0.2 \u03bcg\/kg per minute) infusion also increased LVFS and LVEF in transgenic mice more than in control mice (LVFS, 59\u00b14% versus 47\u00b13%; LVEF, 93\u00b12% versus 85\u00b13%;\n            <jats:italic>P<\/jats:italic>\n            &lt;.05). Heart rates of transgenic mice were higher than those of control mice during ISO and NE infusion. In three transgenic mice with heart rates held constant, LV dP\/dt rose by 33\u00b12% with ISO (0.02 \u03bcg\/kg per minute) and by only 13\u00b12% in three wild-type control mice (\n            <jats:italic>P<\/jats:italic>\n            &lt;.01). NE (0.1 \u03bcg\/kg per minute) also induced a greater effect on LV dP\/dt in the three transgenic mice with heart rates held constant compared with three wild-type control mice (65\u00b18% versus 28\u00b14%,\n            <jats:italic>P<\/jats:italic>\n            &lt;.05). Pathological and histological analyses of older transgenic mouse hearts (16.0\u00b10.8 months old) revealed hypertrophy, degeneration, atrophy of cells, and replacement fibrosis reflected by significant increases in collagen volume in the subendocardium (5.2\u00b11.4% versus 1.2\u00b10.3%,\n            <jats:italic>P<\/jats:italic>\n            &lt;.05) and in the cross-sectional area of myocytes (298\u00b129 versus 187\u00b112 \u03bcm\n            <jats:sup>2<\/jats:sup>\n            ,\n            <jats:italic>P<\/jats:italic>\n            &lt;.05) compared with control mouse hearts. These results suggest that G\n            <jats:sub>s\u03b1<\/jats:sub>\n            overexpression enhances the efficacy of the \u03b2-adrenergic receptor\u2013G\n            <jats:sub>s<\/jats:sub>\n            \u2013adenylyl cyclase signaling pathway. This in turn leads to augmented inotropic and chronotropic responses to endogenous sympathetic stimulation. This action over the life of the animal results in myocardial damage characterized by cellular degeneration, necrosis, and replacement fibrosis, with the remaining cells undergoing compensatory hypertrophy. As a model, this transgenic mouse offers new insights into the mechanisms of cardiomyopathy and heart failure and provides a new tool for their study.\n          <\/jats:p>","DOI":"10.1161\/01.res.78.4.517","type":"journal-article","created":{"date-parts":[[2012,6,12]],"date-time":"2012-06-12T00:47:05Z","timestamp":1339462025000},"page":"517-524","update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":182,"title":["Adverse Effects of Chronic Endogenous Sympathetic Drive Induced by Cardiac G\n            <sub>s\u03b1<\/sub>\n            Overexpression"],"prefix":"10.1161","volume":"78","author":[{"given":"Mitsunori","family":"Iwase","sequence":"first","affiliation":[{"name":"From the Department of Medicine, Harvard Medical School, Brigham &amp; Women\u2019s Hospital, Boston, Mass; the New England Regional Primate Research Center, Southborough, Mass; the Department of Pathology, University of Alabama, Birmingham; the Department of Molecular and Cellular Biology, The Edison Institute, Ohio University, Athens; and COR Therapeutics Inc, San Francisco, Calif."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sanford P.","family":"Bishop","sequence":"additional","affiliation":[{"name":"From the Department of Medicine, Harvard Medical School, Brigham &amp; Women\u2019s Hospital, Boston, Mass; the New England Regional Primate Research Center, Southborough, Mass; the Department of Pathology, University of Alabama, Birmingham; the Department of Molecular and Cellular Biology, The Edison Institute, Ohio University, Athens; and COR Therapeutics Inc, San Francisco, Calif."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masami","family":"Uechi","sequence":"additional","affiliation":[{"name":"From the Department of Medicine, Harvard Medical School, Brigham &amp; Women\u2019s Hospital, Boston, Mass; the New England Regional Primate Research Center, Southborough, Mass; the Department of Pathology, University of Alabama, Birmingham; the Department of Molecular and Cellular Biology, The Edison Institute, Ohio University, Athens; and COR Therapeutics Inc, San Francisco, Calif."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dorothy E.","family":"Vatner","sequence":"additional","affiliation":[{"name":"From the Department of Medicine, Harvard Medical School, Brigham &amp; Women\u2019s Hospital, Boston, Mass; the New England Regional Primate Research Center, Southborough, Mass; the Department of Pathology, University of Alabama, Birmingham; the Department of Molecular and Cellular Biology, The Edison Institute, Ohio University, Athens; and COR Therapeutics Inc, San Francisco, Calif."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Richard P.","family":"Shannon","sequence":"additional","affiliation":[{"name":"From the Department of Medicine, Harvard Medical School, Brigham &amp; Women\u2019s Hospital, Boston, Mass; the New England Regional Primate Research Center, Southborough, Mass; the Department of Pathology, University of Alabama, Birmingham; the Department of Molecular and Cellular Biology, The Edison Institute, Ohio University, Athens; and COR Therapeutics Inc, San Francisco, Calif."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Raymond K.","family":"Kudej","sequence":"additional","affiliation":[{"name":"From the Department of Medicine, Harvard Medical School, Brigham &amp; Women\u2019s Hospital, Boston, Mass; the New England Regional Primate Research Center, Southborough, Mass; the Department of Pathology, University of Alabama, Birmingham; the Department of Molecular and Cellular Biology, The Edison Institute, Ohio University, Athens; and COR Therapeutics Inc, San Francisco, Calif."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David C.","family":"Wight","sequence":"additional","affiliation":[{"name":"From the Department of Medicine, Harvard Medical School, Brigham &amp; Women\u2019s Hospital, Boston, Mass; the New England Regional Primate Research Center, Southborough, Mass; the Department of Pathology, University of Alabama, Birmingham; the Department of Molecular and Cellular Biology, The Edison Institute, Ohio University, Athens; and COR Therapeutics Inc, San Francisco, Calif."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas E.","family":"Wagner","sequence":"additional","affiliation":[{"name":"From the Department of Medicine, Harvard Medical School, Brigham &amp; Women\u2019s Hospital, Boston, Mass; the New England Regional Primate Research Center, Southborough, Mass; the Department of Pathology, University of Alabama, Birmingham; the Department of Molecular and Cellular Biology, The Edison Institute, Ohio University, Athens; and COR Therapeutics Inc, San Francisco, Calif."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yoshihiro","family":"Ishikawa","sequence":"additional","affiliation":[{"name":"From the Department of Medicine, Harvard Medical School, Brigham &amp; Women\u2019s Hospital, Boston, Mass; the New England Regional Primate Research Center, Southborough, Mass; the Department of Pathology, University of Alabama, Birmingham; the Department of Molecular and Cellular Biology, The Edison Institute, Ohio University, Athens; and COR Therapeutics Inc, San Francisco, Calif."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Charles J.","family":"Homcy","sequence":"additional","affiliation":[{"name":"From the Department of Medicine, Harvard Medical School, Brigham &amp; Women\u2019s Hospital, Boston, Mass; the New England Regional Primate Research Center, Southborough, Mass; the Department of Pathology, University of Alabama, Birmingham; the Department of Molecular and Cellular Biology, The Edison Institute, Ohio University, Athens; and COR Therapeutics Inc, San Francisco, Calif."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephen F.","family":"Vatner","sequence":"additional","affiliation":[{"name":"From the Department of Medicine, Harvard Medical School, Brigham &amp; Women\u2019s Hospital, Boston, Mass; the New England Regional Primate Research Center, Southborough, Mass; the Department of Pathology, University of Alabama, Birmingham; the Department of Molecular and Cellular Biology, The Edison Institute, Ohio University, Athens; and COR Therapeutics Inc, San Francisco, Calif."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","reference":[{"key":"e_1_3_2_1_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI117843"},{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1096\/fasebj.5.9.1650314"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1161\/res.77.3.632"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1161\/01.CIR.58.6.1072"},{"key":"e_1_3_2_5_2","unstructured":"Xiao Y-F Cui Y Vatner DE Ishikawa Y Wagner TE Wight DC Homcy CJ Vatner SF Cantiello HF. Enhancement of cardiac Ca2+ and Cl\u2212 currents in transgenic mice overexpressing Gs\u03b1. Circulation. 1995;92(suppl I):I-432. Abstract."},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.89.22.11051"},{"key":"e_1_3_2_7_2","doi-asserted-by":"publisher","DOI":"10.1038\/358334a0"},{"key":"e_1_3_2_8_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0021-9258(19)74464-0"},{"key":"e_1_3_2_9_2","doi-asserted-by":"publisher","DOI":"10.1161\/res.65.3.2527639"},{"key":"e_1_3_2_10_2","first-page":"H590","volume":"262","year":"1992","unstructured":"Robbins RJ, Swain JL. C-myc protooncogene modulates cardiac hypertrophic growth in transgenic mice. Am J Physiol.. 1992;262:H590-H597.","journal-title":"Am J Physiol."},{"key":"e_1_3_2_11_2","doi-asserted-by":"publisher","DOI":"10.1161\/circ.92.4.978"},{"key":"e_1_3_2_12_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM198207223070401"},{"key":"e_1_3_2_13_2","doi-asserted-by":"publisher","DOI":"10.1161\/res.78.4.511"},{"key":"e_1_3_2_14_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.8160017"},{"key":"e_1_3_2_15_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.7761854"},{"key":"e_1_3_2_16_2","doi-asserted-by":"publisher","DOI":"10.1093\/cvr\/27.9.1606"},{"key":"e_1_3_2_17_2","unstructured":"Dies F Krell MJ Whitlow P Liang C-S Goldenberg I Applefeld MM Gilbert EM. Intermittent dobutamine in ambulatory out-patients with chronic cardiac failure. Circulation. 1986;74(suppl II):II-38. Abstract."},{"key":"e_1_3_2_18_2","doi-asserted-by":"publisher","DOI":"10.1016\/0002-8703(86)90475-8"},{"key":"e_1_3_2_19_2","doi-asserted-by":"publisher","DOI":"10.1161\/circ.69.2.6140091"},{"key":"e_1_3_2_20_2","doi-asserted-by":"publisher","DOI":"10.1016\/0140-6736(90)91517-E"},{"key":"e_1_3_2_21_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM199111213252103"},{"key":"e_1_3_2_22_2","doi-asserted-by":"publisher","DOI":"10.1161\/circ.79.3.2537158"},{"key":"e_1_3_2_23_2","doi-asserted-by":"publisher","DOI":"10.1161\/circ.80.3.2548768"},{"key":"e_1_3_2_24_2","doi-asserted-by":"publisher","DOI":"10.1016\/0735-1097(94)90174-0"},{"key":"e_1_3_2_25_2","doi-asserted-by":"publisher","DOI":"10.1016\/0735-1097(95)00012-S"},{"key":"e_1_3_2_26_2","doi-asserted-by":"publisher","DOI":"10.1038\/374421a0"}],"container-title":["Circulation Research"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.ahajournals.org\/doi\/full\/10.1161\/01.RES.78.4.517","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,5,12]],"date-time":"2024-05-12T20:30:09Z","timestamp":1715545809000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.ahajournals.org\/doi\/10.1161\/01.RES.78.4.517"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[1996,4]]},"references-count":26,"journal-issue":{"issue":"4","published-print":{"date-parts":[[1996,4]]}},"alternative-id":["10.1161\/01.RES.78.4.517"],"URL":"https:\/\/doi.org\/10.1161\/01.res.78.4.517","relation":{},"ISSN":["0009-7330","1524-4571"],"issn-type":[{"value":"0009-7330","type":"print"},{"value":"1524-4571","type":"electronic"}],"subject":[],"published":{"date-parts":[[1996,4]]},"assertion":[{"value":"1995-09-11","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"1996-01-05","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"1996-04-01","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}