Maternal Nutrient Restriction Reduces Carotid Artery Constriction Without Increasing Nitric Oxide Synthesis in the Late Gestation Rat Fetus

Abstract

Chronic reduction in substrate delivery to the fetus may induce redistribution of fetal cardiac output to maintain nutrient delivery to vital organs, including the brain. Reduced vasoconstriction, in conjunction with increased local synthesis of nitric oxide may contribute to "brain sparing." The authors hypothesized that maternal undernutrition would reduce vasoconstrictor responses in fetal carotid arteries due to increased nitric oxide. Timed pregnant Sprague-Dawley rats were randomized on day 0 of pregnancy to control (C) or nutrient restricted (NR) diet. Dams were killed on day 20 of pregnancy. Fetal carotid artery responses were assessed using a pressurized myograph system. Fetal body weight was reduced by NR diet. In NR fetuses, liver, lung, kidney, and heart weights were lower, whereas proportional brain weight was greater. Carotid artery constriction to endothelin-1 was similar in both groups; however, phenylephrineinduced constriction was decreased in NR arteries. Arteries from control fetuses constricted in response to increasing concentrations of L-NAME, whereas arteries from NR did not. There was also no effect of L-NAME on constriction to phenylephrine in arteries from NR fetuses. Our study indicates that the reduced carotid artery vasoconstriction to phenylephrine in NR fetuses, which is consistent with the maintenance of fetal brain blood flow, was not mediated by enhanced nitric oxide. Reduced phenylephrine but not endothelin-1-induced constriction suggests specific effects on adrenergic carotid artery function, which may implicate this pathway in the vascular adaptation to fetal undernutrition. Intrauterine growth restriction (IUGR) involves a failure of the fetus to achieve its genetic potential for growth. Fetal growth restriction has significant impact on pregnancy outcome and neonatal health status where IUGR fetuses demonstrate increased neonatal mortality, morbidity, and prematurity rates (1,2). The pathophysiological processes that result in fetal growth restriction are multiple and diverse; globally one cause of growth restriction is thought to be malnutrition. Human populations studied after acute maternal malnutrition during pregnancy have demonstrated both impaired fetal growth and long-term consequences for adult health (3-7).Compromised fetuses undergo cardiovascular adaptation to preserve blood flow to vital organs, such as the heart, brain, and adrenal glands, at the expense of peripheral tissues (8,9). This adaptation may involve changes in the regional vascular response to vasoconstrictor, and dilator factors, which serves to redistribute cardiac output. It has previously been demonstrated in fetal sheep that maternal nutrient restriction impaired endothelial-dependent relaxation, and vascular sensitivity to nitric oxide in small arteries from the femoral vascular bed (10,11); however, the effects of undernutrition on the function of arteries supplying blood flow to the brain are not known.During acute hypoxia, the fetal redistribution of cardiac output, and maintenance of brai...

Prenatal hypoxia independent of undernutrition promotes molecular markers of insulin resistance in adult offspring

“…In the present study, birth weight was significantly reduced in both hypoxic and pair-fed offspring in comparison to the control offspring, which supports previous studies in rats (27)(28)(29)(30)(31)(32)(33). Hypoxic and pair-fed offspring were not only of low birth weight but also showed a reduced BMI relative to controls.…”

Brain apoptosis and carotid artery reactivity in fetal asphyctic preconditioning

“…Accordingly, several studies demonstrated adrenergic-mediated contractions in isolated carotid arteries from fetal and neonatal lambs (26,28) (29). In fetal and neonatal rat carotid arteries, mounted in a pressurized myograph system, adrenergic agonists induced some reduction in lumen diameter (30,31). However our present data indicate that these diameter changes are probably not accompanied by a significant increase in carotid wall tension.…”

Uteroplacental Insufficiency and Lactational Environment Separately Influence Arterial Stiffness and Vascular Function in Adult Male Rats

“…25 For some models of maternal nutrient restriction, impaired contraction to ␣-adrenoceptor stimulation has also been reported in femoral arteries of young male and female offspring 36 and carotid arteries of fetuses. 37 Evidence from growth restriction and maternal undernutrition models indicates that the effect on offspring vascular contraction is variable, region specific, sex dependent, and sometimes agonist specific. 34,[36][37][38] The endothelium plays a central role in the regulation of vascular tone.…”

“…37 Evidence from growth restriction and maternal undernutrition models indicates that the effect on offspring vascular contraction is variable, region specific, sex dependent, and sometimes agonist specific. 34,[36][37][38] The endothelium plays a central role in the regulation of vascular tone. Endothelial dysfunction is evident in humans born small and in experimental models of growth restriction and maternal undernutrition.…”