Dataset Information

PVP formulated fullerene (C60) increases Rho-kinase dependent vascular tissue contractility in pregnant Sprague Dawley rats.

ABSTRACT: Pregnancy is a unique physiological state, in which C60 fullerene is reported to be distributed in both maternal and fetal tissues. Tissue distribution of C60 differs between pregnant and non-pregnant states, presumably due to functional changes in vasculature during pregnancy. We hypothesized that polyvinylpyrrolidone (PVP) formulated C60 (C60/PVP) increases vascular tissue contractility during pregnancy by increasing Rho-kinase activity. C60/PVP was administered intravenously to pregnant and non-pregnant female Sprague Dawley rats. Vascular responses were assessed using wire myography 24h post-exposure. Increased stress generation was observed in uterine artery, thoracic aorta and umbilical vein. Rho-Rho-kinase mediated force maintenance was increased in arterial segments from C60/PVP exposed pregnant rats when compared to PVP exposed rats. Our findings suggest that intravenous exposure to C60/PVP during pregnancy increases vascular tissue contractility of the uterine artery through elements of Rho-Rho-kinase signaling during late stages of pregnancy.

SUBMITTER: Vidanapathirana AK

PROVIDER: S-EPMC4312756 | biostudies-literature | 2014 Nov

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

PVP formulated fullerene (C60) increases Rho-kinase dependent vascular tissue contractility in pregnant Sprague Dawley rats.

Vidanapathirana Achini K AK Thompson Leslie C LC Mann Erin E EE Odom Jillian T JT Holland Nathan A NA Sumner Susan J SJ Han Li L Lewin Anita H AH Fennell Timothy R TR Brown Jared M JM Wingard Christopher J CJ

Reproductive toxicology (Elmsford, N.Y.) 20140801

Pregnancy is a unique physiological state, in which C60 fullerene is reported to be distributed in both maternal and fetal tissues. Tissue distribution of C60 differs between pregnant and non-pregnant states, presumably due to functional changes in vasculature during pregnancy. We hypothesized that polyvinylpyrrolidone (PVP) formulated C60 (C60/PVP) increases vascular tissue contractility during pregnancy by increasing Rho-kinase activity. C60/PVP was administered intravenously to pregnant and n ...[more]

PMID: 25088243

Similar Datasets

Project description:Pregnancy induces maternal renal adaptations that include increased glomerular filtration rate and renal blood flow which can be compromised in obstetrical complications such as preeclampsia. Brown Norway (BN) rat pregnancies are characterized by placental insufficiency, maternal hypertension, and proteinuria. We hypothesized that BN pregnancies would show renal functional, anatomical, or molecular features of preeclampsia. We used the Sprague-Dawley (CD) rat as a model of normal pregnancy. Pregnancy increased the glomerular filtration rate by 50% in CD rats and 12.2% in BN rats compared to non-pregnancy, and induced proteinuria only in BN rats. BN pregnancies showed a decrease in maternal plasma calcitriol levels, which correlated with renal downregulation of 1-alpha hydroxylase and upregulation of 24-hydroxylase. RNA sequencing revealed that pregnancy induced 297 differentially expressed genes (DEGs) in CD rats and 174 DEGs in BN rats, indicating a 70% increased response to pregnancy in CD compared to BN rats. Pregnancy induced activation of innate immune pathways such as ‘Role of Pattern Recognition Receptors’, and ‘Interferon signaling’ with interferon regulatory factor 7 as a common upregulated upstream factor in both rat strains. Comparison of rat strain transcriptomic profiles revealed 475 DEGs at non-pregnancy and 569 DEGs at pregnancy with 205 DEGs shared at non-pregnancy (36%), indicating that pregnancy interacted with rat strain in regulating 64% of the DEGs. Pathway analysis revealed that pregnancy induced a switch in renal transcriptomics in BN rats from ‘inhibition of renal damage’ to ‘acute phase reaction’, ‘recruitment of immune cells’ and ‘inhibition of 1,25-(OH)2-vitamin D synthesis’. Key upstream regulators included peroxisome-proliferator-activated receptor alpha (PPARA), platelet-derived growth factor B dimer (PDGF-BB), and NF-kB p65 (RELA). DNA methylome profiling by reduced representation bisulfite sequencing studies revealed that the DEGs did not correlate with changes in promoter methylation. In sum, BN rat kidneys respond to pregnancy-specific signals with an increase in pro-inflammatory gene networks and alteration of metabolic pathways including vitamin D deficiency in association with mild proteinuria and blunted GFR increase. However, the lack of glomerular endotheliosis and mild hypertension/proteinuria in pregnant BN rats limits the relevance of this rat strain for preeclampsia research.

Project description: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 ?g/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/mm2 increase 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.

Dataset Information

PVP formulated fullerene (C60) increases Rho-kinase dependent vascular tissue contractility in pregnant Sprague Dawley rats.

Publications

PVP formulated fullerene (C60) increases Rho-kinase dependent vascular tissue contractility in pregnant Sprague Dawley rats.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets