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In conscious animals before CHF, Ang II produced a load-dependent slowing of the time constant of LV relaxation (\u03c4) and did not depress intact LV contractile function. After CHF, although Ang II produced a similar increase in LV systolic pressure, the increases in LV diastolic pressure and time constant \u03c4 were much greater, and contractile performance was depressed. These changes persisted when the elevation of end-systolic pressure was prevented by nitroprusside. Similar changes were also present after autonomic blockade. In isolated myocytes, before CHF, Ang II (10<jats:sup>\u22126<\/jats:sup>mol\/L) produced a slight positive inotropic effect. In contrast, after CHF, Ang II produced a negative inotropic effect and slowed the rate of relengthening. The effects in the intact LV and myocytes were reversed by an Ang II AT<jats:sub>1<\/jats:sub>receptor blocker (losartan). We conclude that pacing-induced CHF alters the LV and myocyte response to Ang II, so that Ang II produces direct depressions in intact LV contraction, relaxation, and filling and exacerbates myocyte contractile dysfunction. These effects are mediated through the activation of AT<jats:sub>1<\/jats:sub>receptors.<\/jats:p>","DOI":"10.1161\/01.res.78.5.880","type":"journal-article","created":{"date-parts":[[2012,6,12]],"date-time":"2012-06-12T00:47:05Z","timestamp":1339462025000},"page":"880-892","update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":72,"title":["Altered Ventricular and Myocyte Response to Angiotensin II in Pacing-Induced Heart Failure"],"prefix":"10.1161","volume":"78","author":[{"given":"Che-Ping","family":"Cheng","sequence":"first","affiliation":[{"name":"From the Section of Cardiology, Bowman Gray School of Medicine, Wake Forest University, Winston-Salem, NC."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Makoto","family":"Suzuki","sequence":"additional","affiliation":[{"name":"From the Section of Cardiology, Bowman Gray School of Medicine, Wake Forest University, Winston-Salem, NC."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nobuyuki","family":"Ohte","sequence":"additional","affiliation":[{"name":"From the Section of Cardiology, Bowman Gray School of Medicine, Wake Forest University, Winston-Salem, NC."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michiya","family":"Ohno","sequence":"additional","affiliation":[{"name":"From the Section of Cardiology, Bowman Gray School of Medicine, Wake Forest University, Winston-Salem, NC."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zhong-Min","family":"Wang","sequence":"additional","affiliation":[{"name":"From the Section of Cardiology, Bowman Gray School of Medicine, Wake Forest University, Winston-Salem, NC."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"William C.","family":"Little","sequence":"additional","affiliation":[{"name":"From the Section of Cardiology, Bowman Gray School of Medicine, Wake Forest University, Winston-Salem, NC."}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"276","reference":[{"key":"e_1_3_2_1_2","doi-asserted-by":"publisher","DOI":"10.1161\/circ.74.5.2945673"},{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1093\/cvr\/26.8.783"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1161\/res.71.1.1606661"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1161\/circ.92.3.562"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1016\/0735-1097(92)90130-F"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.1161\/res.73.3.8348688"},{"key":"e_1_3_2_7_2","doi-asserted-by":"publisher","DOI":"10.1161\/res.73.3.8348686"},{"key":"e_1_3_2_8_2","doi-asserted-by":"publisher","DOI":"10.1161\/circ.90.3.8087951"},{"key":"e_1_3_2_9_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM198706043162301"},{"key":"e_1_3_2_10_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM199108013250501"},{"key":"e_1_3_2_11_2","doi-asserted-by":"publisher","DOI":"10.1016\/0735-1097(93)90482-G"},{"key":"e_1_3_2_12_2","doi-asserted-by":"crossref","unstructured":"Dzau VJ. 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