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We sought to determine whether ANG II stimulates heart growth and cardiomyocyte hypertrophy and\/or hyperplasia in utero in the immature fetal heart independent of the effects on cardiac afterload. In twin gestation, fetal sheep at \u223c100 days gestation (term 145 days), one fetus received a chronic (6 days) infusion of ANG II alone (50 \u03bcg\u00b7kg<jats:sup>\u22121<\/jats:sup>\u00b7min<jats:sup>\u22121<\/jats:sup>) or ANG II plus nitroprusside (NTP) to attenuate the increase in blood pressure; noninstrumented twins served as controls. ANG II alone, but not ANG II + NTP resulted in a significant increase in heart mass (left and right ventricle + septum, corrected for body weight) compared with controls. ANG II, but not ANG II+NTP, also significantly increased cardiomyocyte area compared with control and increased the percentage of binucleated myocytes. ANG II with or without concomitant infusion of NTP increased cardiac PCNA expression, a marker of proliferation. Steady-state protein expression of terminal mitogen-activated protein kinases, cyclin B1, cyclin E1, and p21 were similar among groups. We conclude that in vivo, ANG II increases fetal cardiac mass via cardiomyocyte hypertrophy, differentiation, and to a lesser extent hyperplasia. The effects of ANG II on hypertrophy appear dependent upon the increase in blood pressure (mechanical load), whereas effects on proliferation are load-independent.<\/jats:p>","DOI":"10.1152\/ajpregu.00034.2015","type":"journal-article","created":{"date-parts":[[2015,3,26]],"date-time":"2015-03-26T10:24:30Z","timestamp":1427365470000},"page":"R965-R972","source":"Crossref","is-referenced-by-count":7,"title":["ANG II modulation of cardiac growth and remodeling in immature fetal sheep"],"prefix":"10.1152","volume":"308","author":[{"given":"Jeremy","family":"Sandgren","sequence":"first","affiliation":[{"name":"Stead Family Department of Pediatrics, University of Iowa Carver College of Medicine, Iowa City, Iowa"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Thomas D.","family":"Scholz","sequence":"additional","affiliation":[{"name":"Stead Family Department of Pediatrics, University of Iowa Carver College of Medicine, Iowa City, 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