Chorionic plate arterial function is altered in maternal obesity

Hayward, Christina; Higgins, Lucy; Cowley, Elizabeth; Greenwood, Susan; Mills, Thomas M.; Sibley, Colin P.; Wareing, Mark

doi:10.1016/j.placenta.2013.01.001

Cited by 25 publications

(24 citation statements)

References 39 publications

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“…The EC 50 of insulin was 1.8 ± 0.2 nM and the effect was abolished by preincubation with N -ethylmaleimide (NEM) and L-lysine, both competitive inhibitors of transport system y + for cationic amino acid (González et al, 2011). Now, we confirmed that insulin induced relaxation in chorionic plate veins and in fetal-side of placental vascular bed, decreasing the vasoconstriction induced by U46619 and H 2 O 2 , stimuli that had previously been shown to have vasoconstrictor effects in chorionic plate arteries (Beckman and Koppenol, 1996; Hayward et al, 2013). …”

Section: Discussionsupporting

confidence: 82%

Insulin Induces Relaxation and Decreases Hydrogen Peroxide-Induced Vasoconstriction in Human Placental Vascular Bed in a Mechanism Mediated by Calcium-Activated Potassium Channels and L-Arginine/Nitric Oxide Pathways

et al. 2016

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HIGHLIGHTS Short-term incubation with insulin increases the L-arginine transport in HUVECs.Short-term incubation with insulin increases the NO synthesis in HUVECs.Insulin induces relaxation in human placental vascular bed.Insulin attenuates the constriction induced by hydrogen peroxide in human placenta.The relaxation induced by insulin is dependent on BKCa channels activity in human placenta. Insulin induces relaxation in umbilical veins, increasing the expression of human amino acid transporter 1 (hCAT-1) and nitric oxide synthesis (NO) in human umbilical vein endothelial cells (HUVECs). Short-term effects of insulin on vasculature have been reported in healthy subjects and cell cultures; however, its mechanisms remain unknown. The aim of this study was to characterize the effect of acute incubation with insulin on the regulation of vascular tone of placental vasculature. HUVECs and chorionic vein rings were isolated from normal pregnancies. The effect of insulin on NO synthesis, L-arginine transport, and hCAT-1 abundance was measured in HUVECs. Isometric tension induced by U46619 (thromboxane A2 analog) or hydrogen peroxide (H2O2) were measured in vessels previously incubated 30 min with insulin and/or the following pharmacological inhibitors: tetraethylammonium (KCa channels), iberiotoxin (BKCa channels), genistein (tyrosine kinases), and wortmannin (phosphatidylinositol 3-kinase). Insulin increases L-arginine transport and NO synthesis in HUVECs. In the placenta, this hormone caused relaxation of the chorionic vein, and reduced perfusion pressure in placental cotyledons. In vessels pre-incubated with insulin, the constriction evoked by H2O2 and U46619 was attenuated and the effect on H2O2-induced constriction was blocked with tetraethylammonium and iberiotoxin, but not with genistein, or wortmannin. Insulin rapidly dilates the placental vasculature through a mechanism involving activity of BKCa channels and L-arginine/NO pathway in endothelial cells. This phenomenon is related to quick increases of hCAT-1 abundance and higher capacity of endothelial cells to take up L-arginine and generate NO.

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Section: Discussionsupporting

confidence: 82%

Insulin Induces Relaxation and Decreases Hydrogen Peroxide-Induced Vasoconstriction in Human Placental Vascular Bed in a Mechanism Mediated by Calcium-Activated Potassium Channels and L-Arginine/Nitric Oxide Pathways

et al. 2016

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“…Systemic or placental infl ammation may also result in endothelial dysfunction. Pre-gravid obesity increases maternal levels of markers of endothelial dysfunction [ 39 ] and is associated with impaired vascular function in placental arteries [ 17 ]. Consequently, this may impact upon fetal heart development, because uteroplacental circulation has been linked with fetal vascular function [ 40 ].…”

Section: Placental Inflammation In Maternal Obesitymentioning

confidence: 99%

The Role of Placental Inflammasomes in Linking the Adverse Effects of Maternal Obesity on Fetal Development

Aye

Lager

Powell

2015

Metabolic Syndrome and Complications of Pregnancy

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“…Arterial sections (2 mm) were mounted on a Danish Myotechnology M610 wire myograph (Danish Myotech, Aarhus, Denmark), normalized to an internal diameter of 0.9 of L 13.3 kPa (luminal pressure ;45 mmHg) and left to equilibrate (378C; gassed with air containing 5% CO 2 ) in 6 ml physiological salt solution [31] (PSS: 119 mM NaCl, 25 mM NaHCO 3 , 4.69 mM KCl, 2.4 mM MgSO 4 , 1.6 mM CaCl 2 , 1.18 mM KH 2 PO 4 , 6.05 mM glucose, and 0.034 mM ethylenediaminetetraacetic acid, pH 7.4) as previously described [32]. Vessel viability was assessed using a high potassium solution [31] (KPSS: 11 mM NaCl, 25 mM NaHCO 3 , 120 mM KCl, 2.4 mM MgSO 4 , 1.6 mM CaCl 2 , 1.18 mM KH 2 PO 4 , 6.05 mM glucose, and 0.034 mM ethylenediaminetetraacetic acid, pH 7.4). Protocol 1 was used to assess vascular function in MAs from all three BMI groups.…”

Section: Wire Myographymentioning

confidence: 99%

Maternal Obesity Impairs Specific Regulatory Pathways in Human Myometrial Arteries1

Hayward

Cowley

Mills

et al. 2014

Biology of Reproduction

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Obese women (body mass index ≥30 kg/m(2)) are at greater risk than normal weight women of pregnancy complications associated with maternal and infant morbidity, particularly the development of cardiovascular disease and metabolic disorders in later life; why this occurs is unknown. Nonpregnant, obese individuals exhibit systemic vascular endothelial dysfunction. We tested the hypothesis that obese pregnant women have altered myometrial arterial function compared to pregnant women of normal (18-24 kg/m(2)) and overweight (25-29 kg/m(2)) body mass index. Responses to vasoconstrictors, U46619 (thromboxane mimetic) and arginine vasopressin, and vasodilators, bradykinin and the nitric oxide donor sodium nitroprusside, were assessed by wire myography in myometrial arteries from normal weight (n = 18), overweight (n = 18), and obese (n = 20) women with uncomplicated pregnancies. Thromboxane-prostanoid receptor expression was assessed using immunostaining in myometrial arteries of normal weight and obese women. Vasoconstriction and vasodilatation were impaired in myometrial arteries from obese women with otherwise uncomplicated pregnancies. Disparate agonist responses suggest that vascular function in obese women is not globally dysregulated but may be specific to thromboxane and nitric oxide pathways. Because obesity rates are escalating, it is important to identify the mechanisms underlying impaired vascular function and establish why some obese women compensate for vascular dysfunction and some do not. Future studies are needed to determine whether central adiposity results in an altered endocrine milieu that may promote vascular dysfunction by altering the function of perivascular adipose tissue.

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Chorionic plate arterial function is altered in maternal obesity

Cited by 25 publications

References 39 publications

Insulin Induces Relaxation and Decreases Hydrogen Peroxide-Induced Vasoconstriction in Human Placental Vascular Bed in a Mechanism Mediated by Calcium-Activated Potassium Channels and L-Arginine/Nitric Oxide Pathways

Insulin Induces Relaxation and Decreases Hydrogen Peroxide-Induced Vasoconstriction in Human Placental Vascular Bed in a Mechanism Mediated by Calcium-Activated Potassium Channels and L-Arginine/Nitric Oxide Pathways

The Role of Placental Inflammasomes in Linking the Adverse Effects of Maternal Obesity on Fetal Development

Maternal Obesity Impairs Specific Regulatory Pathways in Human Myometrial Arteries1

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