Developmental Exposure to Indoor Flame Retardants Disrupts Sympathetic and Hypothalamic‐Pituitary‐Adrenal (HPA) Axis Activity in Osmotic Challenged Rats

Abstract

Research in our lab has demonstrated that perinatal exposure to the polybrominated‐dipheyl ether (PBDE) mixture, DE‐71, triggers pressor responses to hyperosmotic stress in adult rats. To evaluate the effect of ganglionic blockade (GB), dams were dosed with DE‐71 or corn‐oil daily from gestational day 4 through postnatal day (PND) 21. At PND 60 offspring received hyperosmotic (3.5 M NaCl) or normosmotic NaCl (0.9g%) i.p. with or without pentolinium (19.2mg/kg). After 3 hours, blood pressure was measured as % Δ baseline using sphygmomanometry under anesthesia. Hyperosmotic treatment produced a significant increase in systolic BP in PBDE‐rats compared to oil‐controls (22.99+ 2.55 vs 1.53+2.25%, n=22; p<0.001). GB partially occluded the pressor response in PBDE hyperosmotic rats, (12.85+1.30%, n=12; p<0.01), suggesting involvement of sympathetic nervous system (SNS). Adrenal catecholamine (CA) content, measured via fluorometric detection, was significantly reduced in PBDE hyperosmotic vs normosmotic rats (5.4+1.3 vs. 1.3+0.4 mM; n=21, p<0.05), suggesting exaggerated CA release. This was not compensated for by increased mRNA levels for TH, PNMT or PACAP mRNA. Plasma corticosterone was significantly elevated in PBDE hyperosmotic rats vs controls suggesting HPA overactivation. Adrenal HPA markers appeared to rise in the PBDE hyperosmotic rats, but this was not significant.In conclusion, adult hyperosmotic treatment in rats exposed to PBDEs perinatally show disrupted SNS and CA balance and hyperactive HPA axis. Our findings reveal that PBDEs may target endocrine and autonomic systems associated with stress responses.