Department of Cell Biology and Neuroscience, University of California, Riverside, CA 92521, USA.
Toxicol Appl Pharmacol. 2011 Oct 15;256(2):103-13. doi: 10.1016/j.taap.2011.07.014. Epub 2011 Jul 29.
Polybrominated diphenyl ethers (PBDEs) and the structurally similar chemicals polychlorinated biphenyls (PCBs) disrupt the function of multiple endocrine systems. PCBs and PBDEs disrupt the secretion of vasopressin (VP) from the hypothalamus during osmotic activation. Since the peripheral and central vasopressinergic axes are critical for osmotic and cardiovascular regulation, we examined whether perinatal PBDE exposure could impact these functions during physiological activation. Rats were perinatally dosed with a commercial PBDE mixture, DE-71. Dams were given 0 (corn oil control), 1.7 (low dose) or 30.6 mg/kg/day (high dose) in corn oil from gestational day (GD) 6 through postnatal day (PND) 21 by oral gavage. In the male offspring exposed to high dose PBDE plasma thyroxine and triiodothyronine levels were reduced at PND 21 and recovered to control levels by PND 60 when thyroid stimulating hormone levels were elevated. At 14-18 months of age, cardiovascular responses were measured in four groups of rats: Normal (Oil, normosmotic condition), Hyper (Oil, hyperosmotic stress), Hyper PBDE low (1.7 mg/kg/day DE-71 perinatally, hyperosmotic stress), and Hyper PBDE high (30.6 mg/kg/day DE-71 perinatally, hyperosmotic stress). Systolic blood pressure (BP), diastolic BP, and heart rate (HR) were determined using tail cuff sphygmomanometry and normalized to pretreatment values (baseline) measured under basal conditions. Hyperosmotic treatment yielded significant changes in systolic BP in PBDE exposed rats only. Hyper PBDE low and high dose rats showed 36.1 and 64.7% greater systolic BP responses at 3h post hyperosmotic injection relative to pretreatment baseline, respectively. No treatment effects were measured for diastolic BP and HR. Hyper and Hyper PBDE rats showed increased mean plasma osmolality values by 45 min after injection relative to normosmotic controls. In contrast to Hyper rats, Hyper PBDE (high) rats showed a further increase in mean plasma osmolality at 3h (358.3±12.4mOsm/L) relative to 45 min post hyperosmotic injection (325.1±11.4mOsm/L). Impaired osmoregulation in PBDE-treated animals could not be attributed to decreased levels of plasma vasopressin. Our findings suggest that developmental exposure to PBDEs may disrupt cardiovascular reactivity and osmoregulatory responses to physiological activation in late adulthood.
多溴联苯醚（PBDEs）和结构相似的化学物质多氯联苯（PCBs）会破坏多个内分泌系统的功能。PCBs 和 PBDEs 会破坏渗透压激活时下丘脑血管加压素（VP）的分泌。由于外周和中枢血管加压素能轴对于渗透压和心血管调节至关重要，我们研究了围产期 PBDE 暴露是否会在生理激活期间影响这些功能。大鼠在围产期接受了一种商业 PBDE 混合物 DE-71 的处理。从妊娠第 6 天（GD）到产后第 21 天（PND），通过口服灌胃，母鼠接受 0（玉米油对照）、1.7（低剂量）或 30.6mg/kg/天（高剂量）的玉米油。在接受高剂量 PBDE 暴露的雄性后代中，PND 21 时血浆甲状腺素和三碘甲状腺原氨酸水平降低，而 PND 60 时甲状腺刺激激素水平升高，恢复到对照水平。在 14-18 个月大时，对四组大鼠进行了心血管反应测量：正常（油，等渗条件）、高渗（油，高渗应激）、高渗 PBDE 低（1.7mg/kg/天 DE-71 围产期，高渗应激）和高渗 PBDE 高（30.6mg/kg/天 DE-71 围产期，高渗应激）。通过尾套测压法测量收缩压（BP）、舒张压（DBP）和心率（HR），并将其归一化为在基础条件下测量的预处理值（基线）。高渗透压处理仅导致 PBDE 暴露大鼠的收缩压发生显著变化。高渗 PBDE 低剂量和高剂量组大鼠在高渗透压注射后 3 小时的收缩压反应分别比预处理基线增加 36.1%和 64.7%。舒张压和 HR 未检测到治疗作用。与等渗对照组相比，注射后 45 分钟，高渗和高渗 PBDE 大鼠的平均血浆渗透压值分别增加了 45 分钟和 64.7%。与高渗大鼠不同，高渗 PBDE（高）大鼠在高渗透压注射后 3 小时（358.3±12.4mOsm/L）的平均血浆渗透压进一步升高，与高渗透压注射后 45 分钟（325.1±11.4mOsm/L）相比。在 PBDE 处理的动物中，渗透压调节受损不能归因于血浆血管加压素水平降低。我们的研究结果表明，发育期暴露于 PBDEs 可能会破坏成年后期对生理激活的心血管反应和渗透压调节反应。
