Oxidative stress as common trait of endothelial dysfunction in chorionic arteries from fetuses with IUGR and LGA.
BACKGROUND
Fetal macrosomia and intrauterine growth restriction (IUGR) associate with increased morbidity in the neonate. Placental vascular relaxation is impaired in fetal macrosomia, as well as in IUGR, and this could result from increased oxidative stress present in both conditions. We determined the role of pro- and anti-oxidants on NOS dependent relaxation in placental chorionic arteries from pregnancies with LGA babies from overweight and/or obese mothers (LOOM) and IUGR fetuses from normal BMI women.


METHODS
Chorionic arteries were mounted in a wire-myograph, where responses to the NOS-dependent agent CGRP in presence or absence of the antioxidant N-acetyl cysteine (NAC), the pro-oxidant SIN-1, the SOD inhibitor DDC, and the GPx inhibitor MS were determined. Additionally the presence of pro- and antioxidant enzymes (NOX-4, SOD-1, SOD-2 and GPx-1) and eNOS in chorionic and umbilical vessels were addressed by immunohistochemistry.


RESULTS
Maximal CGRP-induced relaxation was comparable to controls but presented a reduced potency in chorionic arteries from LOOM placentae, whilst in IUGR vessels both maximal response and potency were reduced. NAC increased maximal relaxation in controls, IUGR and LOOM arteries, whilst SIN-1 completely abolished the CGRP-induced relaxation only in IUGR and LOOM samples, the later effect was paralleled by SOD or GPx inhibition. These responses associated with the presence of NOX-4, SOD-1 and GPx-1 in the endothelium and vascular wall of chorionic and umbilical arteries in the different groups studied.


CONCLUSIONS
These data suggest that NOS dependent relaxation in placental vessels from IUGR and LOOM pregnancies present a higher sensitivity to oxidative stress.
Division of Obstetrics & Gynecology, Faculty of Medicine, Pontificia Universidad Católica de Chile, Santiago, Chile.
D
D
Schneider
Division of Obstetrics & Gynecology, Faculty of Medicine, Pontificia Universidad Católica de Chile, Santiago, Chile; Division of Pediatrics, Faculty of Medicine, Pontificia Universidad Católica de Chile, Santiago, Chile.
C
C
Hernández
Division of Obstetrics & Gynecology, Faculty of Medicine, Pontificia Universidad Católica de Chile, Santiago, Chile.
M
M
Farías
Division of Pediatrics, Faculty of Medicine, Pontificia Universidad Católica de Chile, Santiago, Chile.
R
R
Uauy
Division of Obstetrics & Gynecology, Faculty of Medicine, Pontificia Universidad Católica de Chile, Santiago, Chile.
B J
BJ
Krause
Division of Obstetrics & Gynecology, Faculty of Medicine, Pontificia Universidad Católica de Chile, Santiago, Chile; Division of Pediatrics, Faculty of Medicine, Pontificia Universidad Católica de Chile, Santiago, Chile. Electronic address: pcasane@uc.cl.
P
P
Casanello
D000328:Adult; D000975:Antioxidants / Q000378:metabolism; D001158:Arteries / Q000378:metabolism / Q000503:physiopathology*; D016022:Case-Control Studies; D004730:Endothelium, Vascular / Q000503:physiopathology*; D005260:Female; D005317:Fetal Growth Retardation / Q000503:physiopathology*; D005320:Fetal Macrosomia / Q000503:physiopathology*; D005979:Glutathione Peroxidase / Q000378:metabolism; D006801:Humans; D066298:In Vitro Techniques; D000074663:NADPH Oxidase 4; D019255:NADPH Oxidases / Q000378:metabolism; D052250:Nitric Oxide Synthase Type III / Q000378:metabolism; D009765:Obesity / Q000503:physiopathology*; D018384:Oxidative Stress; D010920:Placenta / Q000503:physiopathology; D011247:Pregnancy; D013482:Superoxide Dismutase / Q000378:metabolism; D000072105:Superoxide Dismutase-1; D000094765:Glutathione Peroxidase GPX1; D000099156:Superoxide Dismutase 2
D000975:Antioxidants; D005979:Glutathione Peroxidase; D000074663:NADPH Oxidase 4; D019255:NADPH Oxidases; D052250:Nitric Oxide Synthase Type III; D013482:Superoxide Dismutase; D000072105:Superoxide Dismutase-1; D000094765:Glutathione Peroxidase GPX1; D000099156:Superoxide Dismutase 2; C000606290:SOD1 protein, human; C496314:NOS3 protein, human; C498910:NOX4 protein, human; C000722067:GPX1 protein, human
Endothelial function; IUGR; LGA; Maternal obesity; Oxidative stress