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Fetal Physiological Programming

Differential effects of maternal hypoxia or nutrient restriction on carotid and femoral vascular function in neonatal rats

¹Perinatal Research Centre, Departments of Obstetrics and Gynecology, and Physiology, University of Alberta, Edmonton, Canada; and ²Department of Physiology, Centre for the Early Origins of Adult Health, School of Molecular and Biomedical Science, University of Adelaide, South Australia, Australia

Submitted 18 March 2004 ; accepted in final form 2 November 2004

In response to reduced oxygen or nutrient supply, the fetus may redistribute cardiac output to conserve brain and heart growth, at the expense of the peripheral tissues; however, it is not known whether alterations in vascular function are maintained after birth or whether reduced fetal oxygen versus nutrient supply produces distinct effects. Using a pressure myograph, we examined isolated carotid and femoral artery responses to phenylephrine and endothelin-1 in neonatal rats, after either reduced maternal oxygen or global nutrient restriction during late gestation. Timed-pregnant Sprague-Dawley rats were randomly assigned to control (n = 10), hypoxia (12% O₂, n = 9), or nutrient restriction (NR, 40% of control diet, n = 7) protocol and treated from day 15–21 of pregnancy. Pups were collected 3–12 h after birth. Neonatal weights (P < 0.001) and relative liver weights (P < 0.001) were lower in hypoxia and nutrient restriction treatments compared with control, while relative heart weights were greater in the hypoxia than in the control or nutrient restriction groups (P < 0.01). Constriction to phenylephrine was reduced in carotid arteries from the hypoxia and nutrient restriction groups compared with control (P < 0.001), while the femoral artery response was greater in hypoxia-treated neonates compared with control or nutrient-restricted neonates (P < 0.01). Only the hypoxia reduced carotid responses to endothelin-1, while no differences were observed in the endothelin-1 responses in femoral arteries. Maternal hypoxia and maternal nutrient restriction produced distinct effects on heart growth and neonatal vascular function, suggesting that regional changes in cardiovascular function after poor fetal growth are dependent on the nature of the insult in utero.

fetal growth; oxygen; artery; endothelin-1; phenylephrine

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