title: Effects of propranolol on heart rate and development in Japanese medaka (Oryzias latipes) and zebrafish (Danio rerio).
abstract: Propranolol is a β-adrenergic receptor antagonist (β-blocker) that is frequently used to treat hypertension and other cardiovascular conditions in humans. Detected in surface waters due to discharge of domestic wastewater, propranolol has demonstrated significant species differences in toxicity between fish. The aim of this study was to investigate the effects of propranolol on heart rate and development in embryos of two species of fish; Japanese medaka (JM) Oryzias latipes and zebrafish (ZF) Danio rerio. Parents and fertilized embryos of each species were exposed to nominal (measured) concentrations of 0.1 (0.09), 1 (1.1) and 10 (8.3) μg/L of propranolol. Heart rate was monitored during subsequent exposure in embryos at incremental developmental periods (44, 54, 64 h post-fertilization (hpf) for ZF and 68, 116, 164 hpf for JM). Heart development and morphology was examined using whole mount immunostaining with distance measurements between the sinus venosus (SV) and bulbus arteriosis (BV). Morphological measurements were made at 44 hpf for ZF and 164 hpf for JM. In ZF, a significant reduction in heart rate was observed at 0.08 μg/L propranolol, along with an increase in the SV-BA distance at 44 hpf. Significant reductions in heart rate were also observed in ZF at 54 and 64 hpf at all concentrations of propranolol. For JM, heart rates generally decreased at all developmental timepoints (68, 116 and 164 hpf) after propranolol treatment, with concentration dependent decreases observed at 164 hpf and a lowest observed effect concentration (LOEC) of 0.09 μg/L propranolol at each timepoint. However, significant alterations in cardiac morphology were not observed in JM at 164 hpf. In contrast, heart rates and morphology in ZF were affected with a non-monotonic concentration response in morphology and a LOEC of 0.09 μg/L propranolol for morphological alterations at 44 hpf and for heart rate at each timepoint. These data indicated unique developmental stages of susceptibility between species and that combined parental and embryo exposures may lead to greater impairment of cardiac development and function in offspring than separate exposures of adults and embryos.
authors: Department of Environmental Sciences, University of California, Riverside, CA 92521, United States.
authors: Juliane
authors: J
authors: Finn
authors: Michelle
authors: M
authors: Hui
authors: Vincent
authors: V
authors: Li
authors: Varenka
authors: V
authors: Lorenzi
authors: Nayeli
authors: N
authors: de la Paz
authors: Shuk Han
authors: SH
authors: Cheng
authors: Leo
authors: L
authors: Lai-Chan
authors: Daniel
authors: D
authors: Schlenk
mesh_terms: D000818:Animals; D004625:Embryo, Nonmammalian / Q000187:drug effects; D006321:Heart / Q000033:anatomy & histology / Q000187:drug effects* / Q000196:embryology; D006339:Heart Rate / Q000187:drug effects*; D009990:Oryzias / Q000502:physiology*; D011433:Propranolol / Q000633:toxicity*; D014874:Water Pollutants, Chemical / Q000633:toxicity*; D015027:Zebrafish / Q000502:physiology*
chemical_list: D014874:Water Pollutants, Chemical; D011433:Propranolol