title: Intrauterine undernutrition: expression and activity of the endothelial nitric oxide synthase in male and female adult offspring.
abstract: OBJECTIVE
  Epidemiological studies suggest that intrauterine undernutrition plays an important role in the development of arterial hypertension in adulthood. In an attempt to define the mechanisms whereby blood pressure may be raised, we have hypothesized that arteries from offspring of nutritionally restricted dams exhibit abnormalities in the endothelial function and in nitric oxide synthesis. In order to investigate the existence of potential gender differences on the effects of intrauterine undernutrition, both male and female offspring of pregnant Wistar rats on normal and restricted diets were studied in adulthood.
  
  
  METHODS
  Female pregnant Wistar rats were fed either normal or 50% of the normal intake diets, during the whole gestational period. At 14 weeks of age, the rats were used for the study of vascular reactivity, eNOS and iNOS gene expression, eNOS activity and, in the case of females, estrogen levels.
  
  
  RESULTS
  Intrauterine undernutrition induced hypertension in both male and female offspring, but hypertension was more severe in male rats. Endothelium-intact aortic rings from male and female rats in the restricted diet group exhibited increased responses to norepinephrine, decreased vasodilation to acetylcholine and unaltered responses to sodium nitroprusside in comparison to aortic rings from control rats. No gender-related differences were observed in the vascular reactivity studies. Intrauterine undernutrition promoted decreased gene expression for eNOS in aorta isolated from male, but not female, offspring, reduction in eNOS activity in both male and female offspring and impairment in synthesis of estrogen in female offspring.
  
  
  CONCLUSIONS
  Our data show that intrauterine undernutrition: (1) induces hypertension both in the male and female offspring, hypertension being more severe in male than in female rats; (2) alters endothelium-dependent responses in aortas from the resulting offspring. The endothelial dysfunction is associated with a decrease in activity/expression of eNOS in aortas from male offspring. The mechanism involved in altered response to ACh in female offspring might be a consequence of reduction in estrogen levels leading to reduced eNOS activity.
authors.affiliation: Laboratory of Hypertension, Department of Pharmacology, Institute of Biomedical Science, University of São Paulo, Av. Prof Lineu Prestes, 1524- São Paulo, SP, Brazil.
authors.forename: Maria do Carmo P
authors.initials: Mdo C
authors.lastname: Franco
authors.forename: Robéria Maria M P
authors.initials: RM
authors.lastname: Arruda
authors.forename: Ana Paula Villela
authors.initials: AP
authors.lastname: Dantas
authors.forename: Elisa Mitiko
authors.initials: EM
authors.lastname: Kawamoto
authors.forename: Zuleica B
authors.initials: ZB
authors.lastname: Fortes
authors.forename: Cristoforo
authors.initials: C
authors.lastname: Scavone
authors.forename: Maria Helena C
authors.initials: MH
authors.lastname: Carvalho
authors.forename: Rita C A
authors.initials: RC
authors.lastname: Tostes
authors.forename: Dorothy
authors.initials: D
authors.lastname: Nigro
mesh_terms: D000109:Acetylcholine; D000375:Aging / Q000502:physiology*; D000818:Animals; D001011:Aorta; D001794:Blood Pressure; D004305:Dose-Response Relationship, Drug; D004730:Endothelium, Vascular / Q000378:metabolism*; D004967:Estrogens / Q000097:blood; D005260:Female; D005317:Fetal Growth Retardation / Q000201:enzymology*; D066298:In Vitro Techniques; D008297:Male; D009119:Muscle Contraction; D009131:Muscle, Smooth, Vascular / Q000503:physiopathology; D019001:Nitric Oxide Synthase / Q000235:genetics / Q000378:metabolism*; D052247:Nitric Oxide Synthase Type II; D052250:Nitric Oxide Synthase Type III; D012333:RNA, Messenger / Q000032:analysis; D011897:Random Allocation; D051381:Rats; D017208:Rats, Wistar; D012723:Sex; D014665:Vasodilator Agents
chemical_list: D004967:Estrogens; D012333:RNA, Messenger; D014665:Vasodilator Agents; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; D052250:Nitric Oxide Synthase Type III; C496318:Nos2 protein, rat; C496316:Nos3 protein, rat; D000109:Acetylcholine