Effect of endothelium-derived relaxing factor inhibition on theumbilical-placental circulation in fetal lambs in utero

Chang, Jia-Kan; Roman, Christine; Heymann, Michaël

doi:10.1016/0002-9378(92)91704-e

Cited by 72 publications

(41 citation statements)

References 21 publications

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“…Chang et al reported that' basal NO release plays an important role in maintaining the low vascular tone in the intact umbilical-placental circulation (26). These data suggest that baseline constitutive levels ofNO may play a direct role in the maintenance of vascular relaxation.…”

Section: Resultsmentioning

confidence: 88%

Nitric oxide regulates the expression of vasoconstrictors and growth factors by vascular endothelium under both normoxia and hypoxia.

Kourembanas¹,

McQuillan²,

Leung³

et al. 1993

J. Clin. Invest.

419

230

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The mechanisms by which hypoxia causes vasoconstriction in vivo are not known. Accumulating evidence implicates the endothelium as a key regulator of vascular tone. Hypoxia induces the expression and secretion of endothelin-1 (ET-1), a potent vasoconstrictor in cultured human endothelial cells. We report here that nitric oxide (NO), an endothelial-derived relaxing factor, modifies this induction of ET-1. Whereas low oxygen tension (Po2 = 20-30 Torr) increases ET-1 expression four-to eightfold above that seen at normal oxygen tension (Po2 = 150 Torr), sodium nitroprusside, which releases NO, suppresses this effect. This inhibition of hypoxia-induced ET-1 expression occurs within the first hour of exposure of cells to sodium nitroprusside. Moreover, when the endogenous constitutive levels of NO made by endothelial cells are suppressed using N-w-nitro-L-arginine, a potent competitive inhibitor of NO synthase, the baseline levels of ET-1 produced in normoxic environments are increased three-to fourfold. The effects of hypoxia and the NO synthase inhibitor on ET-1 expression are additive. The regulation of ET-1 production by NO appears to be at the level of transcription. Similar effects of NO were observed on the expression of the PDGF-B chain gene. PDGF-B expression was suppressed by NO in a hypoxic environment and induced by N-w-nitro-L-arginine in both normoxic and hypoxic environments. These findings suggest that in addition to its role as a vasodilator, NO may also influence vascular tone via the regulated reciprocal production ofET-1 and PDGF-B in the vasculature. (J. Clin. Invest. 1993. 92:99-104.) Key words: hypoxianitric oxide * endothelin * umbilical vein * platelet-derived growth factor-B Introduction Endothelial cells serve a key role in the local regulation ofblood vessel tone via the release of vasoactive agents controlling smooth muscle cell proliferation and contractility. They are known to release both vasoconstrictors such as endothelin-1 (ET-1) 1 ( 1 ) and PDGF (2) and vasodilators such as endothelial-derived nitric oxide (NO) (3) in response to local and circulating factors. In fact, the presence of an intact endothelium

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Section: Resultsmentioning

confidence: 88%

Nitric oxide regulates the expression of vasoconstrictors and growth factors by vascular endothelium under both normoxia and hypoxia.

Kourembanas¹,

McQuillan²,

Leung³

et al. 1993

J. Clin. Invest.

419

230

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“…9 The importance of basal NO release in maintaining low vascular resistance in the fetoplacental circulation in humans has been shown in human placental arteries and perfused placental cotyledons in vitro, 10,11 and in sheep, where NOS inhibition increases fetoplacental vascular resistance in vivo. 12 In addition, eNOS-derived NO may also maintain low fetoplacental vascular resistance by promoting angiogenesis…”

mentioning

confidence: 99%

Endothelial NO Synthase Augments Fetoplacental Blood Flow, Placental Vascularization, and Fetal Growth in Mice

et al. 2013

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Abstract-It is not known whether eNOS deficiency in the mother or the conceptus (ie, placenta and fetus) causes fetal growth restriction in mice lacking the endothelial NO synthase gene (eNOS knockout [KO]). We hypothesized that eNOS sustains fetal growth by maintaining low fetoplacental vascular tone and promoting fetoplacental vascularity and that this is a conceptus effect and is independent of maternal genotype. We found that eNOS deficiency blunted fetal growth, and blunted the normal increase in umbilical blood flow and umbilical venous diameter and the decrease in umbilical arterial Resistance Index in late gestation (14.5-17.5 days) in eNOS KO relative to C57Bl/6J controls. On day 17.5, fetoplacental capillary lobule length and capillary density in vascular corrosion casts were reduced in eNOS KO placentas. Reduced vascularization may be a result of decreased vascular endothelial growth factor mRNA and protein expression in eNOS KO placentas at this stage. These factors, combined with significant anemia found in eNOS KO fetuses, would be anticipated to reduce fetal oxygen delivery and contribute to the fetal tissue hypoxia that was detected in the heart, lung, kidney, and liver by immunohistochemistry using pimonidazole. Although maternal eNOS deficiency impairs uteroplacental adaptations to pregnancy, maternal genotype was not a significant factor affecting growth in heterozygous conceptuses. This indicates that fetal growth restriction was primarily caused by conceptus eNOS deficiency. In mice, placental hemodynamic and vascular changes with gestation and growth restriction showed strong parallels with human pregnancy. Thus, the eNOS KO model could provide insights into the pathogenesis of human intrauterine growth restriction. and vasculogenesis as shown in other vascular beds studied in adult animals. 13In the current study, we hypothesized that eNOS sustains fetal growth by maintaining low fetoplacental vascular tone and promoting fetoplacental vascularity. We further hypothesized that this is a conceptus effect and is independent of maternal genotype. We used eNOS knockout (KO) pregnancies because eNOS KO fetuses exhibit fetal growth restriction in late gestation, [14][15][16] and pregnant eNOS KO mothers exhibit impaired uteroplacental remodeling and a blunted rise in uteroplacental blood flow and cardiac output. 15,16 However, they neither overexpress sFlt1 mRNA in the placenta 16 nor do they become more hypertensive during pregnancy. [16][17][18] In this study, we quantified umbilical vein blood flow and umbilical artery Resistance Index using micro-ultrasound, visualized the fetoplacental vasculature using vascular corrosion casts, and evaluated hypoxia in the fetus in eNOS KO mice and in the background strain, C57Bl/6J (wild type [WT]). Whether IUGR is secondary to reduced uteroplacental perfusion or is a result of effects of eNOS deficiency in the conceptus in this model is not clear. Thus, crossbreeding experiments were performed to determine the impact of maternal genotype on the fetal phen...

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“…Há lesão endotelial imunorreativa 26 que determina agregação plaquetária e depósito de fibrina no leito vascular renal 27 . A diminuição no fluxo sangüí-neo renal e na taxa de filtração glomerular, assim como o aumento concomitante nas concentrações de renina, de fator natriurético atrial, de angiotensina e de catecolaminas pode resultar em oligúria e insuficiência renal 1 .…”

Section: Sistema Renalunclassified

“…There is an immunoreactive endothelial injury 26 determining platelet aggregation and fibrin deposition on the renal vascular bed 27 . Decreased renal blood flow and glomerular filtration rate, associated to simultaneous increase in rennin concentrations, arterial natriuretic factor, angiotensin and catecholamines may result in oliguria and renal failure 1 .…”

Section: Renal Systemmentioning

confidence: 99%

Anestesia na Pré-Eclâmpsia

Ganem¹,

Castiglia²

2002

Rev. Bras. Anestesiol.

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Effect of endothelium-derived relaxing factor inhibition on theumbilical-placental circulation in fetal lambs in utero

Cited by 72 publications

References 21 publications

Nitric oxide regulates the expression of vasoconstrictors and growth factors by vascular endothelium under both normoxia and hypoxia.

Nitric oxide regulates the expression of vasoconstrictors and growth factors by vascular endothelium under both normoxia and hypoxia.

Endothelial NO Synthase Augments Fetoplacental Blood Flow, Placental Vascularization, and Fetal Growth in Mice

Anestesia na Pré-Eclâmpsia

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