Effects of undernutrition in early pregnancy on systemic small artery function in late-gestation fetal sheep

Ozaki, Takashi; Hawkins, Paul; Nishina, Hiroshige; Steyn, Clare; Poston, Lucilla; Hanson, Mark A.

doi:10.1067/mob.2000.107463

Cited by 56 publications

(52 citation statements)

References 15 publications

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“…In the rat, a moderate nutritional restriction (70% of normal intake) in the first 18 d of pregnancy results in offspring with significant IUGR that catch up in body weight to that of controls by postnatal day 20. These abnormalities increase with age and are most pronounced in male offspring [70] . We have developed rodent models of developmental programming using global maternal undernutrition throughout pregnancy [47,71] .…”

Section: Maternal Undernutritionmentioning

confidence: 97%

Developmental programming of the metabolic syndrome - critical windows for intervention

Vickers

2011

WJG

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Metabolic disease results from a complex interaction of many factors, including genetic, physiological, behavioral and environmental influences. The recent rate at which these diseases have increased suggests that environmental and behavioral influences, rather than genetic causes, are fuelling the present epidemic. In this context, the developmental origins of health and disease hypothesis has highlighted the link between the periconceptual, fetal and early infant phases of life and the subsequent development of adult obesity and the metabolic syndrome. Although the mechanisms are yet to be fully elucidated, this programming was generally considered an irreversible change in developmental trajectory. Recent work in animal models suggests that developmental programming of metabolic disorders is potentially reversible by nutritional or targeted therapeutic interventions during the period of developmental plasticity. This review will discuss critical windows of developmental plasticity and possible avenues to ameliorate the development of postnatal metabolic disorders following an adverse early life environment.

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Section: Maternal Undernutritionmentioning

confidence: 97%

Developmental programming of the metabolic syndrome - critical windows for intervention

Vickers

2011

WJG

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“…and late gestation (10,11). The authors demonstrated that undernutrition impaired endothelial-dependent relaxation without affecting constriction to norepinephrine in branches of the femoral artery (10,11).…”

Section: Carotid Artery Function In the Fetal Ratmentioning

confidence: 99%

“…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.…”

mentioning

confidence: 99%

“…Although vascular dysfunction in peripheral arteries has been demonstrated in rodent and ovine neonatal offspring after manipulation of maternal diet during pregnancy (10,15,16), the effect of maternal nutrient restriction on fetal carotid vascular responses are not known. A comprehensive understanding of the regional changes in vascular function that may arise after reduced fetal growth is critical to understanding the abnormalities of regional blood flow profiles observed in human IUGR pregnancies (17)(18)(19).…”

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confidence: 99%

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

et al. 2005

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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...

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“…11 Also, undernutrition in early pregnancy is associated with decreased endotheliumdependent relaxation in blood vessels of fetal sheep. 12 Although the majority of low-birth-weight infants in the Western world are the result of a reduction in uteroplacental perfusion rather than maternal malnutrition, 13 little is known regarding the renal and vascular mechanisms linking intrauterine growth restriction caused by reduced uteroplacental perfusion and hypertension. In recent studies, we have examined renal and vascular functions in a model of intrauterine growth restriction produced in response to reduced uteroplacental perfusion pressure initiated in late pregnancy.…”

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confidence: 99%

Decreased Endothelium-Dependent NO-cGMP Vascular Relaxation and Hypertension in Growth-Restricted Rats on a High-Salt Diet

2004

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Abstract-Low birth weight caused by placental insufficiency increases the risk of hypertension in young adults, particularly while ingesting a high-salt diet; however, the vascular mechanisms involved are unclear. We tested whether intrauterine fetal growth restriction results in salt-sensitive offspring that exhibit impaired endothelium-dependent relaxation, enhanced vascular contraction, and hypertension during high-salt diet feeding. Male offspring of control pregnant rats and pregnant rats with reduced uterine perfusion pressure (intrauterine growth restricted [IUGR]) were fed either a normal-sodium (NS, 1%) or a high-sodium (HS, 8%) diet. Body weight was less in IUGR/NS and IUGR/HS than in NS and HS rats. Arterial pressure was greater in IUGR/NS (144Ϯ4 mm͉Hg) than in NS (131Ϯ3 mm͉Hg) rats and far greater in IUGR/HS (171Ϯ12 mm͉Hg) than in HS (129Ϯ2 mm͉Hg) rats. In isolated, endothelium-intact aortic strips, phenylephrine (Phe, 10 Ϫ5 mol/L) caused an increase in active stress that was greater in IUGR/NS (13.9Ϯ0.9 N/m 2 ) than in NS (8.5Ϯ0.6 N/m 2 ) animals and far greater in IUGR/HS (18.2Ϯ1.2 N/m 2 ) than in HS (9.4Ϯ0.8x10 4 N/m 2 ) rats. Acetylcholine caused relaxation of the Phe-mediated contraction and induced vascular nitrite/nitrate production that was less in IUGR/NS than in NS animals and far less in IUGR/HS than in HS rats. N G -nitro-L-arginine methyl ester, which inhibits nitric oxide (NO) synthase, or ODQ, which inhibits cGMP production in smooth muscle, inhibited acetylcholine relaxations and enhanced Phe contractions in NS and HS rats but not in IUGR/NS or IUGR/HS rats. Endothelium removal enhanced Phe-induced stress in NS and HS rats but not in IUGR/NS or IUGR/HS rats. Thus, endothelium-dependent relaxation via the NO-cGMP pathway is inhibited in systemic vessels of IUGR rats, particularly during intake of an HS diet. This might explain the increased vasoconstriction and arterial pressure in low-birth-weight offspring during ingestion of an HS diet.

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Effects of undernutrition in early pregnancy on systemic small artery function in late-gestation fetal sheep

Cited by 56 publications

References 15 publications

Developmental programming of the metabolic syndrome - critical windows for intervention

Developmental programming of the metabolic syndrome - critical windows for intervention

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

Decreased Endothelium-Dependent NO-cGMP Vascular Relaxation and Hypertension in Growth-Restricted Rats on a High-Salt Diet

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