caa a22 4500 467978905 CHVBK 20180323112513.0 cr unu---uuuuu 170328e19901101xx s 000 0 eng 10.1007/BF01974690 doi (NATIONALLICENCE)springer-10.1007/BF01974690 Effects of calcium channel blockers on the development of early rat postimplantation embryos in culture [Elektronische Daten] [Gabriele Stein, Mithilesh Srivastava, Hans-Joachim Merker, Diether Neubert] Rat embryos (9.5-day-old) were cultured for 48 h in the presence of nifedipine (NIF), nimodipine (NIM), nitrendipine (NIT), gallopamil HCl (GAL), verapamil HCl (VER) and diltiazem HCl (DIL). The effects on growth and morphogenetic differentiation in vitro were monitored. Dose-response relationships were evaluated, including an assessment of the "no-observed-effect-level” (NOEL) or the "lowest-observed-effect-level” (LOEL), and the lowest concentration tested inducing abnormalities in 100% of the embryos ("100% EL”). The morphological alterations observed at the highest concentrations were very similar for all six drugs. The abnormalities concerned yolk sac circulation and morphology, as well as heartbeat, the morphology of the heart, head, neural tube, or fore-limbs, and the shape of the embryo. The abnormal embryos were also growth retarded (decrease in protein content and crown-rump length). Interference with calcium channel functions seems to represent an interesting model for studying a special kind of abnormal prenatal development, especially the differentiation of certain mesenchymal structures. The concentration ranges between NOELs and 100% ELs were found to be: NIM=0.1-1 Μg/ml; NIT and VER=1-10 Μg/ml; DIL=1-30 Μg/ml, and LOELs-100%ELs were: GAL=1-10 Μg/ml; NIF=10-30 Μg/ml. Springer-Verlag, 1990 Rat whole-embryo culture nationallicence In vitro nationallicence Calcium channel blockers nationallicence Nifedipine nationallicence Nimodipine nationallicence Nitrendipine nationallicence Gallopamil nationallicence Verapamil nationallicence Diltiazem nationallicence NIF : Nifedipine nationallicence NIM : Nimodipine nationallicence NIT : Nitrendipine nationallicence GAL : Gallopamil HCl nationallicence VER : Verapamil HCl nationallicence DIL : Diltiazem HCl nationallicence 100%EL : lowest dose tested inducing abnormalities in 100% of the embryos nationallicence Stein Gabriele Institut für Toxikologie und Embryopharmakologie, Freie Universität Berlin, Garystrasse 5, 1000, Berlin 33 aut Srivastava Mithilesh Institut für Toxikologie und Embryopharmakologie, Freie Universität Berlin, Garystrasse 5, 1000, Berlin 33 aut Merker Hans-Joachim Institut für Toxikologie und Embryopharmakologie, Freie Universität Berlin, Garystrasse 5, 1000, Berlin 33 aut Neubert Diether Institut für Toxikologie und Embryopharmakologie, Freie Universität Berlin, Garystrasse 5, 1000, Berlin 33 aut Archives of Toxicology Springer-Verlag 64/8(1990-11-01), 623-638 0340-5761 64:8<623 1990 64 204 https://doi.org/10.1007/BF01974690 text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1007/BF01974690 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Stein Gabriele Institut für Toxikologie und Embryopharmakologie, Freie Universität Berlin, Garystrasse 5, 1000, Berlin 33 aut NATIONALLICENCE 700 1- Srivastava Mithilesh Institut für Toxikologie und Embryopharmakologie, Freie Universität Berlin, Garystrasse 5, 1000, Berlin 33 aut NATIONALLICENCE 700 1- Merker Hans-Joachim Institut für Toxikologie und Embryopharmakologie, Freie Universität Berlin, Garystrasse 5, 1000, Berlin 33 aut NATIONALLICENCE 700 1- Neubert Diether Institut für Toxikologie und Embryopharmakologie, Freie Universität Berlin, Garystrasse 5, 1000, Berlin 33 aut NATIONALLICENCE 773 0- Archives of Toxicology Springer-Verlag 64/8(1990-11-01), 623-638 0340-5761 64:8<623 1990 64 204 Metadata rights reserved Springer special CC-BY-NC licence nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-springer