title: Altered cardiovascular reactivity and osmoregulation during hyperosmotic stress in adult rats developmentally exposed to polybrominated diphenyl ethers (PBDEs).
abstract: 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.
authors.affiliation: Department of Cell Biology and Neuroscience, University of California, Riverside, CA 92521, USA.
authors.forename: Ashini
authors.initials: A
authors.lastname: Shah
authors.forename: Cary G
authors.initials: CG
authors.lastname: Coburn
authors.forename: Abena
authors.initials: A
authors.lastname: Watson-Siriboe
authors.forename: Rebecca
authors.initials: R
authors.lastname: Whitley
authors.forename: Anoush
authors.initials: A
authors.lastname: Shahidzadeh
authors.forename: Elizabeth R
authors.initials: ER
authors.lastname: Gillard
authors.forename: Robert
authors.initials: R
authors.lastname: Nichol
authors.forename: Martha
authors.initials: M
authors.lastname: Leon-Olea
authors.forename: Mark
authors.initials: M
authors.lastname: Gaertner
authors.forename: Prasada Rao S
authors.initials: PR
authors.lastname: Kodavanti
authors.forename: Margarita C
authors.initials: MC
authors.lastname: Currás-Collazo
mesh_terms: D000367:Age Factors; D000818:Animals; D000831:Animals, Newborn; D001794:Blood Pressure / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D005260:Female; D055768:Halogenated Diphenyl Ethers / Q000009:adverse effects*; D008297:Male; D009997:Osmotic Pressure / Q000187:drug effects*; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects / Q000503:physiopathology; D051381:Rats; D020318:Rats, Long-Evans; D013972:Thyrotropin / Q000097:blood; D013974:Thyroxine / Q000097:blood; D014284:Triiodothyronine / Q000097:blood; D014667:Vasopressins / Q000097:blood; D014882:Water-Electrolyte Balance / Q000187:drug effects*
chemical_list: D055768:Halogenated Diphenyl Ethers; D014284:Triiodothyronine; D014667:Vasopressins; D013972:Thyrotropin; D013974:Thyroxine