Neonatal oxygen exposure in rats leads to cardiovascular and renal alterations in adulthood.
Long-term vascular and renal consequences of neonatal oxidative injury are unknown. Using a rat model, we sought to investigate whether vascular function and blood pressure are altered in adult rats exposed to hyperoxic conditions as neonates. We also questioned whether neonatal O(2) injury causes long-term renal damage, important in the pathogenesis of hypertension. Sprague-Dawley pups were kept with their mother in 80% O(2) or room air from days 3 to 10 postnatal, and blood pressure was measured (tail cuff) from weeks 7 to 15. Rats were euthanized, and vascular reactivity (ex vivo carotid rings), oxidative stress (lucigenin chemiluminescence and dihydroethidium fluorescence), microvascular density (tibialis anterior muscle), and nephron count were studied. In male and female rats exposed to O(2) as newborns, systolic and diastolic blood pressures were increased (by an average of 15 mm Hg); ex vivo, maximal vasoconstriction (both genders) and sensitivity (males only) specific to angiotensin II were increased; endothelium-dependant vasodilatation to carbachol but not to NO-donor sodium nitroprussiate was impaired; superoxide dismutase analogue prevented vascular dysfunction to angiotensin II and carbachol; vascular superoxide production was higher; and capillary density (by 30%) and number of nephrons per kidney (by 25%) were decreased. These data suggest that neonatal hyperoxia leads in the adult rat to increased blood pressure, vascular dysfunction, microvascular rarefaction, and reduced nephron number in both genders. Our findings support the hypothesis of developmental programming of adult cardiovascular and renal diseases and provide new insights into the potential role of oxidative stress in this process.
Department of Pediatrics, Research Center, CHU Sainte-Justine, Université de Montréal, Montreal, Quebec, Canada.
Catherine
C
Yzydorczyk
Blandine
B
Comte
Gilles
G
Cambonie
Jean-Claude
JC
Lavoie
Nathalie
N
Germain
Yue
Y
Ting Shun
Julie
J
Wolff
Christian
C
Deschepper
Rhian M
RM
Touyz
Martine
M
Lelièvre-Pegorier
Anne Monique
AM
Nuyt
D000818:Animals; D000831:Animals, Newborn / Q000502:physiology*; D001794:Blood Pressure / Q000187:drug effects / Q000502:physiology; D002196:Capillaries / Q000187:drug effects; D002318:Cardiovascular Diseases / Q000209:etiology* / Q000503:physiopathology; D002319:Cardiovascular System / Q000187:drug effects* / Q000503:physiopathology; D004195:Disease Models, Animal; D005260:Female; D006339:Heart Rate / Q000187:drug effects / Q000502:physiology; D006973:Hypertension / Q000209:etiology* / Q000503:physiopathology; D007668:Kidney / Q000187:drug effects* / Q000473:pathology; D008297:Male; D009399:Nephrons / Q000187:drug effects; D018384:Oxidative Stress / Q000187:drug effects / Q000502:physiology; D010100:Oxygen / Q000009:adverse effects* / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D017382:Reactive Oxygen Species / Q000378:metabolism
D017382:Reactive Oxygen Species; D010100:Oxygen