Nitric oxide synthase and changes in oxidative stress levels in embryonic kidney observed in a rabbit model of intrauterine growth restriction.
OBJECTIVE
This work aimed to study the effect of uteroplacental circulation restriction on endothelial kidney damage in a fetal rabbit model.


METHODS
New Zealand rabbits were subjected to 40% to 50% of uteroplacental artery ligation at day 25 of pregnancy. After 5 days, surviving fetuses were harvested by cesarean section. The gene and protein expressions of selected enzymes associated with nitric oxide production and oxidative stress were analyzed in fetal kidney homogenates.


RESULTS
The placenta weight (6.06 ± 0.27, p < 0.0319) and fetal body (19.90 ± 1.03, p < 0.0001) were significantly reduced in the uteroplacental circulation restriction group. The kidneys from restricted fetuses presented a mild vascular congestion and glomerular capillary congestion, without inflammation or hypertrophy. We found endothelial nitric oxide synthase phosphorylation inhibition (0.23 ± 0.13, p < 0.012) and arginase-2 (0.29 ± 0.14, p < 0.023) protein induction in fetal kidneys of the circulation restriction group. Finally, the kidneys from circulation-restricted fetuses showed increased inducible nitric oxide synthase messenger RNA (mRNA) (2.68 ± 0.24, p < 0.01) and reduced heme oxygenase-1 mRNA (23 ± 1.3, p < 0.003), with increased reactive oxygen species (1.69 ± 0.09, p < 0.001) and nitrotyrosine protein (1.74 ± 0.28, p < 0.003) levels, without changes in Nox mRNA.


CONCLUSIONS
We describe significant deregulation of vascular activity and oxidative damage in kidneys of fetal rabbits that have been exposed to restriction of the uterine circulation. © 2016 John Wiley & Sons, Ltd.
Department of Obstetrics and Gynecology and Laboratory of Reproductive Biology, Faculty of Medicine, Universidad de los Andes, Santiago, Chile.
Horacio
H
Figueroa
Laboratory of Molecular and Integrative Physiology, Faculty of Medicine, Universidad de los Andes, Santiago, Chile.
Jorge
J
Cifuentes
Laboratory of Molecular and Integrative Physiology, Faculty of Medicine, Universidad de los Andes, Santiago, Chile.
Mauricio
M
Lozano
Faculty of Medicine, Universidad Católica de la Santísima Concepción, Concepción, Chile.|Department of Biological and Chemical Sciences, Universidad San Sebastián, Concepción, Chile.
Cristobal
C
Alvarado
Faculty of Medicine, Universidad Católica de la Santísima Concepción, Concepción, Chile.
Claudia
C
Cabezas
Department of Maternal-Fetal Medicine, Institut Clínic de Ginecologia, Obstetricia i Neonatologia, and Centro de Investigación Biomédica en Red de Enfermedades Raras, Barcelona, Spain.
Elisenda
E
Eixarch
Laboratory of Molecular and Integrative Physiology, Faculty of Medicine, Universidad de los Andes, Santiago, Chile.
Ellio
E
Fernández
Department of Pathological Anatomy, Clínica Universidad de los Andes, Santiago, Chile.
Luis
L
Contreras
Department of Obstetrics and Gynecology and Laboratory of Reproductive Biology, Faculty of Medicine, Universidad de los Andes, Santiago, Chile.
Sebastian E
SE
Illanes
Department of Biological and Chemical Sciences, Universidad San Sebastián, Concepción, Chile.
Edgar
E
Hernández-Andrade
Department of Maternal-Fetal Medicine, Institut Clínic de Ginecologia, Obstetricia i Neonatologia, and Centro de Investigación Biomédica en Red de Enfermedades Raras, Barcelona, Spain.
Eduard
E
Gratacós
Laboratory of Molecular and Integrative Physiology, Faculty of Medicine, Universidad de los Andes, Santiago, Chile.
Carlos E
CE
Irarrazabal
D000818:Animals; D001119:Arginase / Q000378:metabolism*; D004195:Disease Models, Animal; D005260:Female; D005317:Fetal Growth Retardation / Q000235:genetics* / Q000378:metabolism; D051547:Heme Oxygenase-1 / Q000235:genetics* / Q000378:metabolism; D007668:Kidney / Q000378:metabolism / Q000473:pathology; D007678:Kidney Glomerulus / Q000378:metabolism* / Q000473:pathology; D009569:Nitric Oxide / Q000378:metabolism; D019001:Nitric Oxide Synthase / Q000235:genetics* / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II / Q000235:genetics / Q000378:metabolism; D052250:Nitric Oxide Synthase Type III / Q000378:metabolism; D018384:Oxidative Stress / Q000235:genetics*; D010766:Phosphorylation; D021041:Placental Circulation; D011247:Pregnancy; D012333:RNA, Messenger / Q000378:metabolism; D011817:Rabbits; D017382:Reactive Oxygen Species / Q000378:metabolism; D059467:Transcriptome; D014443:Tyrosine / Q000031:analogs & derivatives / Q000378:metabolism
D012333:RNA, Messenger; D017382:Reactive Oxygen Species; D009569:Nitric Oxide; C002744:3-nitrotyrosine; D014443:Tyrosine; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; D052250:Nitric Oxide Synthase Type III; D051547:Heme Oxygenase-1; D001119:Arginase