title: The effect of hypoxia-induced intrauterine growth restriction on renal artery function.
abstract: The risk of developing cardiovascular diseases is known to begin before birth and the impact of the intrauterine environment on subsequent adult health is currently being investigated from many quarters. Following our studies demonstrating the impact of hypoxia in utero and consequent intrauterine growth restriction (IUGR) on the rat cardiovascular system, we hypothesized that changes extend throughout the vasculature and alter function of the renal artery. In addition, we hypothesized that hypoxia induces renal senescence as a potential mediator of altered vascular function. We demonstrated that IUGR females had decreased responses to the adrenergic agonist phenylephrine (PE; pEC50 6.50 ± 0.05 control v. 6.17 ± 0.09 IUGR, P < 0.05) and the endothelium-dependent vasodilator methylcholine (MCh; E max 89.8 ± 7.0% control v. 41.0 ± 6.5% IUGR, P < 0.001). In IUGR females, this was characterised by increased basal nitric oxide (NO) modulation of vasoconstriction (PE pEC50 6.17 ± 0.09 IUGR v. 6.42 ± 0.08 in the presence of the NO synthase inhibitor N-nitro-l-arginine methyl ester hydrochloride (l-NAME; P < 0.01) but decreased activated NO modulation (no change in MCh responses in the presence of l-NAME), respectively. In contrast, IUGR males had no changes in PE or MCh responses but demonstrated increased basal NO (PE pEC50 6.29 ± 0.06 IUGR v. 6.42 ± 0.12 plus l-NAME, P < 0.01) and activated NO (E max 37.8 ± 9.4% control v. -0.8 ± 13.0% plus l-NAME, P < 0.05) modulation. No significant changes were found in gross kidney morphology, proteinuria or markers of cellular senescence in either sex. In summary, renal vascular function was altered by hypoxia in utero in a sex-dependent manner but was unlikely to be mediated by premature renal senescence.
authors.affiliation: 1 Department of Obstetrics and Gynaecology, University of Alberta, Edmonton, Canada.
authors.forename: M T C
authors.initials: MT
authors.lastname: Verschuren
authors.affiliation: 1 Department of Obstetrics and Gynaecology, University of Alberta, Edmonton, Canada.
authors.forename: J S
authors.initials: JS
authors.lastname: Morton
authors.affiliation: 1 Department of Obstetrics and Gynaecology, University of Alberta, Edmonton, Canada.
authors.forename: A
authors.initials: A
authors.lastname: Abdalvand
authors.affiliation: 1 Department of Obstetrics and Gynaecology, University of Alberta, Edmonton, Canada.
authors.forename: Y
authors.initials: Y
authors.lastname: Mansour
authors.affiliation: 3 Women and Children's Health Research Institute and the Cardiovascular Research Centre, Edmonton, Canada.
authors.forename: C F
authors.initials: CF
authors.lastname: Rueda-Clausen
authors.affiliation: 5 Renal Division, Department of Medicine, University of Alberta, Edmonton, Alberta.
authors.forename: C A
authors.initials: CA
authors.lastname: Compston
authors.affiliation: 5 Renal Division, Department of Medicine, University of Alberta, Edmonton, Alberta.
authors.forename: V
authors.initials: V
authors.lastname: Luyckx
authors.affiliation: 1 Department of Obstetrics and Gynaecology, University of Alberta, Edmonton, Canada.
authors.forename: S T
authors.initials: ST
authors.lastname: Davidge
mesh_terms: D000818:Animals; D002794:Choline / Q000031:analogs & derivatives / Q000494:pharmacology; D005260:Female; D005317:Fetal Growth Retardation / Q000209:etiology*; D000860:Hypoxia / Q000150:complications*; D008297:Male; D009569:Nitric Oxide / Q000097:blood; D010656:Phenylephrine / Q000494:pharmacology; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D017207:Rats, Sprague-Dawley; D012077:Renal Artery / Q000502:physiology*
chemical_list: C017506:methylcholine; D010656:Phenylephrine; D009569:Nitric Oxide; D002794:Choline