title: Maternal hypertension induced by NO blockade does not program adult metabolic diseases in growth-restricted rat fetuses.
abstract: OBJECTIVE
  Preeclampsia is a frequent and potentially lethal placental insufficiency pathology causing maternal hypertension and proteinuria, as well as a high rate of intrauterine growth retardation (IUGR) in offspring. Reduced nitric oxide (NO) production may play a role in the mechanisms of this disease. As exposure to adverse early life environment and IUGR has been proposed to increase cardiometabolic diseases risk, we investigated in rats the effects of maternal NO blockade on growth and metabolic phenotype of offspring.
  
  
  METHODS
  Osmotic pumps were implanted in pregnant rats at E17 and diffused saline or L-NAME (50mg/day), a nitric oxide synthesis inhibitor. At birth, IUGR male newborns without limb defects were selected. Body growth, feeding behavior and glucose tolerance were evaluated in offspring. Organs weights, plasma level of several metabolic hormones and genes expressions were determined in fasted 9month-old rats.
  
  
  RESULTS
  L-NAME mothers had elevated blood pressure at E20. Male offspring from L-NAME mothers had a markedly reduced birth weight and developed postnatal catch-up growth during lactation. Some L-NAME newborns presented some limb defects but were not selected in this study (1/3 of all pups). Improved glucose tolerance and hyperphagia after fasting were found in 3-month-old L-NAME rat but not thereafter. In 9-month-old L-NAME rats, a moderate increase of food intake during the light phase and, after fasting, an augmentation of plasma insulin and a reduction of brown adipose tissue (BAT) deposit were found associated with an increased expression of UCP-1 mRNA in this tissue.
  
  
  CONCLUSIONS
  Despite IUGR and postnatal catch up growth, male rats exposed to L-NAME did not develop metabolic diseases when limb defects were not induced by L-NAME. We postulate that maternal hypertension during late gestation is not a major 'programming' metabolic factor for offspring.
authors.affiliation: Université Lille Nord de France, Unité Environnement Périnatal et Croissance, EA 4489, Faculté de Médecine, Pôle Recherche, IFR 114, 59045 Lille. laura.butruille@hotmail.fr
authors.forename: Laura
authors.initials: L
authors.lastname: Butruille
authors.forename: Sylvain
authors.initials: S
authors.lastname: Mayeur
authors.forename: Emmanuelle
authors.initials: E
authors.lastname: Moitrot
authors.forename: Laurent
authors.initials: L
authors.lastname: Storme
authors.forename: Claude
authors.initials: C
authors.lastname: Knauf
authors.forename: Jean
authors.initials: J
authors.lastname: Lesage
authors.forename: Philippe
authors.initials: P
authors.lastname: Deruelle
mesh_terms: D000818:Animals; D000831:Animals, Newborn / Q000378:metabolism*; D001786:Blood Glucose / Q000378:metabolism; D001794:Blood Pressure / Q000187:drug effects / Q000502:physiology; D001835:Body Weight / Q000502:physiology; D004435:Eating / Q000502:physiology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D005317:Fetal Growth Retardation / Q000139:chemically induced / Q000378:metabolism*; D005951:Glucose Tolerance Test; D006973:Hypertension / Q000139:chemically induced / Q000378:metabolism*; D008297:Male; D008659:Metabolic Diseases / Q000139:chemically induced / Q000378:metabolism*; D019331:NG-Nitroarginine Methyl Ester / Q000008:administration & dosage; D009929:Organ Size / Q000502:physiology; D011247:Pregnancy; D011249:Pregnancy Complications, Cardiovascular / Q000139:chemically induced / Q000378:metabolism*; D011297:Prenatal Exposure Delayed Effects / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar
chemical_list: D001786:Blood Glucose; D004791:Enzyme Inhibitors; D019331:NG-Nitroarginine Methyl Ester