title: Transgenerational effect of fetal programming on vascular phenotype and reactivity in endothelial nitric oxide synthase knockout mouse model.
abstract: OBJECTIVE
  The objective of the study was to investigate the transgenerational effect of fetal vascular programming
  
  
  METHODS
  Homozygous NOS3 knockout and wild type controls (NOS3+/+WT) were cross-bred to obtain heterozygous offspring that developed in (KO-/-) mothers lacking a functional NOS3 (KOM) vs wild-type control mothers (KOP). The first-generation KOM(+/-) and KOP(+/-) female mice were then bred with WT(+/+) males to obtain a second generation (F2). F2 offspring were genotyped and WT(+/+)-F2 mice were then used for in vivo blood pressure and in vitro vascular reactivity studies.
  
  
  RESULTS
  WT-F2 mice born to KOM mothers (KOM-F2WT) had significantly higher systolic blood pressure, mean arterial pressure, and pulse pressure, compared with WT-F2 born to KOP mothers. Male KOM-F2WT offspring had significantly increased response to phenylephrine (PE), compared with male KOP-F2WT. Male offspring had increased contractile responses to PE when compared with female. Acetylcholine responses were decreased in female KOM-F2WT, compared with female KOP-F2WT, but the difference was not statistically significant
  
  
  CONCLUSIONS
  Our findings support a transgenerational effect of fetal programming on the vascular phenotype and suggest possible gender specific adaptation.
authors.affiliation: Department of Obstetrics and Gynecology, University of Texas Medical Branch, Galveston, TX 77555-0144, USA. mmcostan@utmb.edu.
authors.forename: Maged M
authors.initials: MM
authors.lastname: Costantine
authors.forename: Labib M
authors.initials: LM
authors.lastname: Ghulmiyyah
authors.forename: Esther
authors.initials: E
authors.lastname: Tamayo
authors.forename: Gary D V
authors.initials: GD
authors.lastname: Hankins
authors.forename: George R
authors.initials: GR
authors.lastname: Saade
authors.forename: Monica
authors.initials: M
authors.lastname: Longo
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D001794:Blood Pressure / Q000235:genetics / Q000502:physiology*; D001835:Body Weight; D005260:Female; D047109:Fetal Development / Q000235:genetics / Q000502:physiology*; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D019001:Nitric Oxide Synthase / Q000172:deficiency; D010641:Phenotype; D014661:Vasoconstriction / Q000235:genetics / Q000502:physiology*
chemical_list: D019001:Nitric Oxide Synthase; D019331:NG-Nitroarginine Methyl Ester
references.citation: BMJ. 1989 Mar 4;298(6673):564-7
references.pmid: 2495113
references.citation: Hypertension. 2001 Feb;37(2 Pt 2):381-5
references.pmid: 11230304
references.citation: Am J Physiol Regul Integr Comp Physiol. 2005 May;288(5):R1114-21
references.pmid: 15626780
references.citation: J Physiol. 2005 Jul 1;566(Pt 1):225-36
references.pmid: 15860532
references.citation: Int J Biochem Cell Biol. 2006;38(5-6):894-903
references.pmid: 16118061
references.citation: Ann N Y Acad Sci. 2002 Jun;966:143-57
references.pmid: 12114268
references.citation: Circulation. 1997 Jul 1;96(1):308-15
references.pmid: 9236450
references.citation: J Hypertens. 2000 Jul;18(7):843-6
references.pmid: 10930180
references.citation: Hum Reprod. 1995 Oct;10(10):2723-30
references.pmid: 8567800
references.citation: Circulation. 1997 Mar 18;95(6):1505-14
references.pmid: 9118519
references.citation: Theriogenology. 2000 Jan 15;53(2):555-74
references.pmid: 10735050
references.citation: Placenta. 2003 Nov;24(10):905-11
references.pmid: 14580372
references.citation: Br J Nutr. 2007 Mar;97(3):435-9
references.pmid: 17313703
references.citation: Curr Opin Cardiol. 1994 Sep;9(5):619-26
references.pmid: 7987043
references.citation: Proc R Soc Lond B Biol Sci. 1963 Oct 22;158:329-42
references.pmid: 14070049
references.citation: Cardiovasc Res. 1999 Aug 15;43(3):788-97
references.pmid: 10690351
references.citation: FASEB J. 1996 Apr;10(5):615-24
references.pmid: 8621060
references.citation: Eur J Hum Genet. 2002 Nov;10(11):682-8
references.pmid: 12404098
references.citation: Curr Biol. 2004 Jul 27;14(14):R546-51
references.pmid: 15268870
references.citation: J Nutr. 2005 Jun;135(6):1382-6
references.pmid: 15930441
references.citation: Clin Sci (Lond). 2008 Mar;114(5):381-92
references.pmid: 17927565
references.citation: Proc R Soc Lond B Biol Sci. 1960 May 17;152:188-206
references.pmid: 13855369
references.citation: Circ Res. 2007 Dec 7;101(12):1225-36
references.pmid: 18063818
references.citation: J Clin Invest. 1999 Feb;103(3):401-6
references.pmid: 9927501
references.citation: Trends Biochem Sci. 2006 Feb;31(2):89-97
references.pmid: 16403636
references.citation: Nutrition. 1997 Sep;13(9):807-13
references.pmid: 9290095
references.citation: Nat Rev Genet. 2007 Apr;8(4):253-62
references.pmid: 17363974
references.citation: Hypertension. 1999 Sep;34(3):372-4
references.pmid: 10489378
references.citation: Hypertension. 2000 May;35(5):1021-4
references.pmid: 10818056
references.citation: Hypertension. 2000 Aug;36(2):195-200
references.pmid: 10948077
references.citation: Nature. 1980 Nov 27;288(5789):373-6
references.pmid: 6253831
references.citation: Bioessays. 2007 Feb;29(2):145-54
references.pmid: 17226802
references.citation: Am J Obstet Gynecol. 1996 Aug;175(2):484-8
references.pmid: 8765273
references.citation: Hypertension. 2001 Apr;37(4):1060-6
references.pmid: 11304503
references.citation: Am J Physiol. 1997 Apr;272(4 Pt 2):H1996-2003
references.pmid: 9139988
references.citation: Nature. 1987 Jun 11-17;327(6122):524-6
references.pmid: 3495737
references.citation: Am J Physiol Regul Integr Comp Physiol. 2005 Jan;288(1):R34-8
references.pmid: 15178540
references.citation: Pharmacol Rev. 1991 Jun;43(2):109-42
references.pmid: 1852778
references.citation: Nature. 2004 Sep 16;431(7006):364-70
references.pmid: 15372044
references.citation: Circulation. 1994 Oct;90(4):1964-8
references.pmid: 7923686
references.citation: Am J Obstet Gynecol. 2003 Jun;188(6):1468-74; discussion 1474-6
references.pmid: 12824980