Antenatal antioxidant prevents adult hypertension, vascular dysfunction, and microvascular rarefaction associated with in utero exposure to a low-protein diet.
Developmental programming of hypertension is associated with vascular dysfunction characterized by impaired vasodilatation to nitric oxide, exaggerated vasoconstriction to ANG II, and microvascular rarefaction appearing in the neonatal period. Hypertensive adults have indices of increased oxidative stress, and newborns that were nutrient depleted during fetal life have decreased antioxidant defenses and increased susceptibility to oxidant injury. To test the hypothesis that oxidative stress participates in early life programming of hypertension, vascular dysfunction, and microvascular rarefaction associated with maternal protein deprivation, pregnant rats were fed a normal, low protein (LP), or LP plus lazaroid (lipid peroxidation inhibitor) isocaloric diet from the day of conception until delivery. Lazaroid administered along with the LP diet prevented blood pressure elevation, enhanced vasomotor response to ANG II, impaired vasodilatation to sodium nitroprusside, and microvascular rarefaction in adult offspring. Liver total glutathione was significantly decreased in LP fetuses, and kidney eight-isoprostaglandin F2alpha (8-isoPGF(2alpha)) levels were significantly increased in adult LP offspring; these modifications were prevented by lazaroid. Renal nitrotyrosine abundance and blood levels of 1,4-dihydroxynonene and 4-hydroxynonenal-protein adducts were not modified by antenatal diet exposure. This study shows in adult offspring of LP-fed dams prevention of hypertension, vascular dysfunction, microvascular rarefaction, and of an increase in indices of oxidative stress by the administration of lazaroid during gestation. Lazaroid also prevented the decrease in antioxidant glutathione levels in fetuses, suggesting an antenatal mild oxidative stress in offspring of LP-fed dams. These studies support the concept that perinatal oxidative insult can lead to permanent alterations in the cardiovascular system development.
Cambonie
Gilles
G
Research Center, Hôpital Sainte-Justine, Department of Pediatrics, University of Montreal, 3175 Côte Sainte-Catherine, Montreal, Quebec, Canada, H3T 1C5.
Comte
Blandine
B
Yzydorczyk
Catherine
C
Ntimbane
Thierry
T
Germain
Nathalie
N
Lê
Ngoc Loan Oanh
NL
Pladys
Patrick
P
Gauthier
Cindy
C
Lahaie
Isabelle
I
Abran
Daniel
D
Lavoie
Jean-Claude
JC
Nuyt
Anne Monique
AM
D000375:Aging / Q000502:physiology*; D000818:Animals; D000831:Animals, Newborn; D000975:Antioxidants / Q000008:administration & dosage / Q000494:pharmacology*; D001808:Blood Vessels / Q000187:drug effects* / Q000503:physiopathology; D018753:Diet, Protein-Restricted / Q000009:adverse effects*; D005260:Female; D006973:Hypertension / Q000209:etiology / Q000473:pathology / Q000503:physiopathology / Q000517:prevention & control; D018384:Oxidative Stress / Q000187:drug effects; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D051381:Rats; D014652:Vascular Diseases / Q000196:embryology / Q000209:etiology / Q000473:pathology / Q000503:physiopathology
D000975:Antioxidants