Developmental defects of coronary vasculature in rat embryos administered bis-diamine and WKY/NCrj rat embryos

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1. A single 200-mg dose of bis-diamine was administered to pregnant Wister rats at 10.5 days of gestation. Fifty-two embryos from 10 mother rats underwent morphological analysis of the coronary arteries. Conotruncal anomalies were detected in 48 of 52 embryos, and an aplastic or hypoplastic left coronary artery was found in all of them.2. Coronary vasculature was first detected in the heart of at 14.5 embryonic day (ED) control rat embryo. However, in the herats of bis-diamine treated embryos, poor promotion of epicardial-endothelial transformation was revealed at ED 14.5, 15.5,16.5, and 17.5, causing abnormal development of the coronary vasculature. V-CAM and tenascine were less expressed in the coronary vascular endothelial cells. Sinusoids were widely and deeply extended in the thin ventricular wall.3. Developmental analysis of the early bis-diamine treated rat embryos using whole embryo culture, disclosed a markedly elongated outflow tract and enlarged ventricle with thin myocardial wall before the truncal division. Histological examinations detected no coronary buds and sparse N-CAM positive cells around the arterial trunk. This was also the case with the early WKY/NCrj rat embryos.4. When bis-diamine was administered to the 10, 11, and 12 pregnant day mother rats, abnormal conotruncal division was seen in 0%, 93%, and 32% of the embryos, respectively. Furthermore, anomalous coronary arteries were detected only when bis-diamine was administered on 11 and 12 pregnant day, and the incidence was coincident with that of anomalous truncal division.Although not being able to clarify whether neural crest cells play a role in coronary bud formation, these studies suggested that abnormal truncal division and pericardial development caused anomalous coronary vascular formation and distribution.