title: Low birth weight followed by postnatal over-nutrition in the guinea pig exposes a predominant player in the development of vascular dysfunction.
abstract: The association between intrauterine growth restriction (IUGR) and hypertension is well established, yet the interaction between IUGR and other pathogenic contributors remains ill-defined. This study examined the independent and interactive effects of fetal growth reduction resulting in low birth weight (LBW), and postnatal Western diet (WD) on vascular function. Growth reduction was induced in pregnant guinea pigs by uterine artery ablation. LBW and normal birth weight (NBW) offspring were randomly assigned to a control diet (CD) or a WD. In young adulthood, length-tension curves were generated in aortic rings and responses to methacholine (MCh) were evaluated in the carotid and aorta using wire myography. Relative to NBW/CD, aortae of NBW/WD offspring were stiffer, as determined by a leftward shift in the length-tension curve, yet the shift in the LBW/CD curve was considerably greater. Aortic stiffening was most severe in LBW/WD (slope: NBW/CD, 1.97 ± 0.04; NBW/WD, 2.16 ± 0.04; LBW/CD, 2.28 ± 0.05; LBW/WD, 2.34 ± 0.07). Maximal responses (Emax) to MCh were significantly blunted in the aorta of LBW/CD vs. NBW/CD (P < 0.05) and in LBW/WD vs. NBW/WD offspring (P < 0.05); but WD alone had no influence on MCh responses. Emax values for carotid responses to MCh were reduced in LBW/CD vs. NBW/CD (P < 0.05). Thus, aortic stiffening was influenced more by LBW than by a postnatal WD and the most severe stiffening was observed in LBW/WD offspring. In contrast, blunted endothelial responses in LBW/CD offspring were not exacerbated by WD. IUGR may have a greater independent impact on vascular function than a postnatal WD.
authors.affiliation: Department of Physiology and Pharmacology, The University of Western London, Ontario, Canada Department of Obstetrics and Gynaecology, The University of Western London, Ontario, Canada jthompson2@gru.edu.
authors.forename: Jennifer A
authors.initials: JA
authors.lastname: Thompson
authors.affiliation: Department of Obstetrics and Gynaecology, The University of Western London, Ontario, Canada Lawson Health Research Institute, The University of Western London, Ontario, Canada Children's Health Research Institute, The University of Western London, Ontario, Canada.
authors.forename: Ousseynou
authors.initials: O
authors.lastname: Sarr
authors.affiliation: Department of Physiology and Pharmacology, The University of Western London, Ontario, Canada.
authors.forename: Karolina
authors.initials: K
authors.lastname: Piorkowska
authors.affiliation: Department of Physiology and Pharmacology, The University of Western London, Ontario, Canada Robarts Research Institute, The University of Western London, Ontario, Canada Department of Medicine, The University of Western London, Ontario, Canada.
authors.forename: Robert
authors.initials: R
authors.lastname: Gros
authors.affiliation: Department of Physiology and Pharmacology, The University of Western London, Ontario, Canada Department of Obstetrics and Gynaecology, The University of Western London, Ontario, Canada Lawson Health Research Institute, The University of Western London, Ontario, Canada Children's Health Research Institute, The University of Western London, Ontario, Canada.
authors.forename: Timothy R H
authors.initials: TR
authors.lastname: Regnault
mesh_terms: D000818:Animals; D001011:Aorta / Q000187:drug effects / Q000503:physiopathology; D001724:Birth Weight; D002339:Carotid Arteries / Q000187:drug effects / Q000503:physiopathology; D066273:Diet, Western / Q000009:adverse effects; D005317:Fetal Growth Retardation / Q000503:physiopathology*; D006168:Guinea Pigs; D016210:Methacholine Chloride / Q000494:pharmacology; D044343:Overnutrition / Q000503:physiopathology*; D059289:Vascular Stiffness
chemical_list: D016210:Methacholine Chloride