title: Flow-mediated vasodilation is impaired in adult rat offspring exposed to prenatal hypoxia.
abstract: There is now a demonstrated association between low birth weight and increased mortality later in life. Changes in fetal development may program the cardiovascular system and lead to an increased risk of cardiovascular diseases later in life. In addition, aging is a risk factor for vascular endothelial-dependent dysfunction. However, the impact of being born intrauterine growth restricted (IUGR) on the normal aging mechanisms of vascular dysfunction is not clear. We hypothesized that IUGR would cause changes in vascular function that would affect the mechanisms of flow-induced vasodilation later in life in an age- or sex-dependent manner. To create an IUGR model, pregnant Sprague-Dawley rats were placed in a hypoxic (11.5% O₂) or control (room air, 21% O₂) environment from days 15 to 21 of pregnancy. Both male and female offspring were investigated at 4 or 12 mo of age. Vascular function was assessed in small mesenteric arteries using flow-induced vasodilation, a physiological stimuli of vasodilation, in a pressure myograph. Flow-induced vasodilation was unaffected at a young age, but was significantly reduced in aging IUGR compared with aging controls (P < 0.05). Underlying vasodilator mechanisms were altered such that nitric oxide-mediated vasodilation was abolished in both young adult and aging IUGR males and females and in aging control females (P > 0.05). Endothelium-derived hyperpolarizing factor-mediated vasodilation was maintained in all groups (P < 0.01). A change in the mechanisms of vasodilation occurring at an earlier age in IUGR offspring may predispose them to develop cardiovascular diseases as an aging adult.
authors.affiliation: Dept. of Obstetrics/Gynaecology and Physiology, Univ. of Alberta, Edmonton, Alberta, Canada.
authors.forename: J S
authors.initials: JS
authors.lastname: Morton
authors.forename: C F
authors.initials: CF
authors.lastname: Rueda-Clausen
authors.forename: S T
authors.initials: ST
authors.lastname: Davidge
mesh_terms: D000375:Aging / Q000502:physiology; D000818:Animals; D001794:Blood Pressure / Q000502:physiology; D004195:Disease Models, Animal; D004730:Endothelium, Vascular / Q000503:physiopathology; D005260:Female; D005317:Fetal Growth Retardation / Q000503:physiopathology*; D000860:Hypoxia / Q000503:physiopathology*; D008297:Male; D008638:Mesenteric Arteries / Q000503:physiopathology*; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D012039:Regional Blood Flow / Q000502:physiology; D012737:Sex Factors; D014664:Vasodilation / Q000502:physiology*