title: Vascular Tissue Contractility Changes Following Late Gestational Exposure to Multi-Walled Carbon Nanotubes or their Dispersing Vehicle in Sprague Dawley Rats.
abstract: Multi-walled carbon nanotubes (MWCNTs) are increasingly used in industry and in nanomedicine raising safety concerns, especially during unique life-stages such as pregnancy. We hypothesized that MWCNT exposure during pregnancy will increase vascular tissue contractile responses by increasing Rho kinase signaling. Pregnant (17-19 gestational days) and non-pregnant Sprague Dawley rats were exposed to 100 μg/kg of MWCNTs by intratracheal instillation or intravenous administration. Vasoactive responses of uterine, mesenteric, aortic and umbilical vessels were studied 24 hours post-exposure by wire myography. The contractile responses of the vessel segments were different between the pregnant and non-pregnant rats, following MWCNT exposure. Maximum stress generation in the uterine artery segments from the pregnant rats following pulmonary MWCNT exposure was increased in response to angiotensin II by 4.9 mN/mm2(+118%), as compared to the naïve response and by 2.6 mN/mm2(+40.7%) as compared to the vehicle exposed group. Following MWCNT exposure, serotonin induced approximately 4 mN/mm2increase in stress generation of the mesenteric artery from both pregnant and non-pregnant rats as compared to the vehicle response. A significant contribution of the dispersion medium was identified as inducing changes in the contractile properties following both pulmonary and intravenous exposure to MWCNTs. Wire myographic studies in the presence of a Rho kinase inhibitor and RhoA and Rho kinase mRNA/protein expression of rat aortic endothelial cells were unaltered following exposure to MWCNTs, suggesting absent/minimal contribution of Rho kinase to the enhanced contractile responses following MWCNT exposure. The reactivity of the umbilical vein was not changed; however, mean fetal weight gain was reduced with dispersion media and MWCNT exposure by both routes. These results suggest a susceptibility of the vasculature during gestation to MWCNT and their dispersion media-induced vasoconstriction, predisposing reduced fetal growth during pregnancy.
authors.affiliation: Department of Physiology, Brody School of Medicine, East Carolina University, NC 27834, USA.
authors.forename: A K
authors.initials: AK
authors.lastname: Vidanapathirana
authors.affiliation: Department of Physiology, Brody School of Medicine, East Carolina University, NC 27834, USA.
authors.forename: L C
authors.initials: LC
authors.lastname: Thompson
authors.affiliation: Department of Physiology, Brody School of Medicine, East Carolina University, NC 27834, USA.
authors.forename: J
authors.initials: J
authors.lastname: Odom
authors.affiliation: Department of Physiology, Brody School of Medicine, East Carolina University, NC 27834, USA.
authors.forename: N A
authors.initials: NA
authors.lastname: Holland
authors.affiliation: Discovery Sciences, RTI International, Research Triangle Park, NC, 27709, USA.
authors.forename: S J
authors.initials: SJ
authors.lastname: Sumner
authors.affiliation: Discovery Sciences, RTI International, Research Triangle Park, NC, 27709, USA.
authors.forename: T R
authors.initials: TR
authors.lastname: Fennell
authors.affiliation: Department of Pharmaceutical Sciences, Skaggs School of Pharmacy and Pharmaceutical Sciences, University of Colorado, CO, 80045, USA.
authors.forename: J M
authors.initials: JM
authors.lastname: Brown
authors.affiliation: Department of Physiology, Brody School of Medicine, East Carolina University, NC 27834, USA.
authors.forename: C J
authors.initials: CJ
authors.lastname: Wingard
keywords: MWCNTs; Nanotoxicology; Pregnancy; Umbilical vein; Uterine artery; Vascular tissue contractility