Antihypertensive drugs methyldopa, labetalol, hydralazine, and clonidine improve trophoblast interaction with endothelial cellular networks in vitro.


OBJECTIVES:The interaction between trophoblasts and maternal endothelium is important for placental vascular modeling. Failure of uterine spiral artery transformation is linked to the etiopathology of preeclampsia. Antihypertensive medications used to control hypertension in early pregnancy can alter placental and circulating cytokines. This study investigated whether selected antihypertensive drugs can modulate the interaction between trophoblast and endothelial cells. METHODS:Human uterine myometrial microvascular endothelial cells were preincubated with (or without) low-dose tumor necrosis factor-α (TNF-α; 0.5 ng/ml) or TNF-α and soluble fms-like tyrosine kinase 1 (sFlt-1; 100 ng/ml). Red fluorescent-labeled endothelial cells were then cultured on Matrigel. After appearance of endothelial cellular networks, green fluorescent-labeled HTR-8/SVneo trophoblast cells were cocultured in the presence of pharmacological doses of methyldopa, labetalol, hydralazine, and clonidine. Images were captured after 24 h and drug effects on HTR-8/SVneo cell integration were quantified by Image Analysis software. The conditioned medium was collected to measure sFlt-1, vascular endothelial growth factor (VEGF), placental growth factor, interleukin-10, and interleukin-6 by ELISA. RESULTS:Methyldopa, labetalol, hydralazine, and clonidine increased trophoblast integration into TNF-α-preincubated endothelial cellular networks. In conditioned medium, sFlt-1 was reduced by methyldopa, hydralazine, and clonidine alone. VEGF was increased by methyldopa. A decrease in placental growth factor was seen by methyldopa and also in nontreated endothelial cell coculture of the other three drugs. CONCLUSION:Some antihypertensive drugs used in pregnancy may improve the cellular interaction between trophoblast and endothelial cells exposed to TNF-α. Methyldopa, hydralazine, and clonidine reduced sFlt-1 concentration in culture medium, whereas labetalol increased trophoblast integration independently of sFlt-1. Methyldopa increased VEGF concentration. Some pregnancy-related antihypertensives may affect placental vascularization.


J Hypertens


Journal of hypertension


Xu B,Charlton F,Makris A,Hennessy A




Has Abstract


2014-05-01 00:00:00


1075-83; discussion 1083










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    abstract::Conscious male beagle dogs were given constant intravenous infusions of noradrenaline for 14 days, four receiving 125 ng/kg/min and four 250 ng/kg/min. Before, during and after these infusions dose-response studies were done in which additional noradrenaline was infused at 500, 1000 and 2000 ng/kg/min, each rate for 1...

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    authors: Casals-Stenzel J,Tree M,Brown JJ,Fraser R,Lever AF,Millar JA,Morton JJ,Robertson JI,Reid JL,Hamilton C

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    authors: Lurbe E,Cifkova R,Cruickshank JK,Dillon MJ,Ferreira I,Invitti C,Kuznetsova T,Laurent S,Mancia G,Morales-Olivas F,Rascher W,Redon J,Schaefer F,Seeman T,Stergiou G,Wühl E,Zanchetti A,European Society of Hypertension.

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    authors: Barnett PA,Spence JD,Manuck SB,Jennings JR

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    abstract:OBJECTIVE:The L/N-type calcium channel blocker (CCB) cilnidipine suppresses sympathetic nerve activity and has a superior renoprotective effect compared with L-type CCBs such as amlodipine. The cardioprotective action of cilnidipine has remained largely uncharacterized, however. We have now investigated the effects of ...

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    authors: Takatsu M,Hattori T,Murase T,Ohtake M,Kato M,Nashima K,Nakashima C,Takahashi K,Ito H,Niinuma K,Aritomi S,Murohara T,Nagata K

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    abstract::Noradrenergic activity was measured in the brainstem, hypothalamus and thoracic spinal cord of male and female spontaneously hypertensive (SHR) and Wistar-Kyoto (WKY) rats at 6 and 28-36 weeks of age. Two techniques were used, measurement of a major noradrenaline (NA) metabolite, free 3,4-dihydroxyphenylethyleneglycol...

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    pub_type: 杂志文章


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    更新日期:1985-06-01 00:00:00

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    authors: Rhee EP,Clish CB,Pierce KA,Saad A,Lerman LO,Textor SC

    更新日期:2015-04-01 00:00:00

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    authors: Haynes RB,Logan AG,Flanagan PT,Milne BJ

    更新日期:1983-06-01 00:00:00

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    pub_type: 杂志文章


    authors: Kotsis V,Stabouli S,Toumanidis S,Tsivgoulis G,Rizos Z,Trakateli C,Zakopoulos N,Sion M

    更新日期:2010-05-01 00:00:00

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    abstract:OBJECTIVE:The prognostic importance of the nocturnal blood pressure (BP) fall and early-morning surge were scarcely investigated in patients with resistant hypertension (RHT). We investigated them in a prospective cohort of 1726 RHT individuals. METHODS:The nocturnal fall and morning surge were calculated from the bas...

    journal_title:Journal of hypertension

    pub_type: 杂志文章


    authors: Cardoso CRL,Salles GF

    更新日期:2021-01-11 00:00:00

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    abstract:OBJECTIVE:In patients with type 2 diabetes mellitus (T2DM), blocking of the renin-angiotensin-aldosterone system (RAAS) has demonstrated efficacy in lowering blood pressure (BP) and urinary albumin excretion rate (UAER). Nonetheless, not all patients successfully respond to RAAS blockade with a reduction in BP and UAER...

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    pub_type: 杂志文章,随机对照试验


    authors: Weir MR,Hollenberg NK,Remuzzi G,Zappe DH,Meng X,Parving HH

    更新日期:2011-10-01 00:00:00

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    abstract:BACKGROUND:Recently, an expert group advised to measure carotid-femoral (cf) pulse wave velocity (PWV) on the right side of the body, and to use a sliding caliper when tape measure distance cannot be obtained in a straight line. The present study investigates the evidence for this advice by comparing the real travelled...

    journal_title:Journal of hypertension

    pub_type: 杂志文章


    authors: Bossuyt J,Van De Velde S,Azermai M,Vermeersch SJ,De Backer TL,Devos DG,Heyse C,Filipovsky J,Segers P,Van Bortel LM

    更新日期:2013-05-01 00:00:00

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    abstract:OBJECTIVE:To evaluate the association between stroke risk and blood pressure (BP) levels with regard to the usage of antihypertensive medications. METHODS:From the Japan arteriosclerosis longitudinal study, 11,371 participants from the four population-based cohort studies (aged 40-89) were followed up for a mean of 9....

    journal_title:Journal of hypertension

    pub_type: 杂志文章,meta分析


    authors: Asayama K,Ohkubo T,Yoshida S,Suzuki K,Metoki H,Harada A,Murakami Y,Ohashi Y,Ueshima H,Imai Y,Japan Arteriosclerosis Longitudinal Study (JALS) group.

    更新日期:2009-02-01 00:00:00

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    pub_type: 杂志文章


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    更新日期:2020-02-01 00:00:00

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    pub_type: 杂志文章


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    pub_type: 杂志文章


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    更新日期:2015-06-01 00:00:00

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    pub_type: 杂志文章


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    更新日期:2011-02-01 00:00:00

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    pub_type: 杂志文章


    authors: Mente A,O'Donnell MJ,Dagenais G,Wielgosz A,Lear SA,McQueen MJ,Jiang Y,Xingyu W,Jian B,Calik KB,Akalin AA,Mony P,Devanath A,Yusufali AH,Lopez-Jaramillo P,Avezum A Jr,Yusoff K,Rosengren A,Kruger L,Orlandini A,Rangar

    更新日期:2014-05-01 00:00:00

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    pub_type: 杂志文章


    authors: Chiu WC,Ho WC,Lin MH,Lee HH,Yeh YC,Wang JD,Chen PC,Health Data Analysis in Taiwan (hDATa) Research Group.

    更新日期:2014-04-01 00:00:00

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    pub_type: 杂志文章


    authors: Liu M,Li Y,Wei FF,Zhang L,Han JL,Wang JG

    更新日期:2013-09-01 00:00:00

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    journal_title:Journal of hypertension

    pub_type: 杂志文章


    authors: Sato A,Suzuki H,Nakazato Y,Shibata H,Inagami T,Saruta T

    更新日期:1994-05-01 00:00:00

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    journal_title:Journal of hypertension

    pub_type: 杂志文章


    authors: Thomas JS,McConnell MF,Bell TG,Padgett GA

    更新日期:1992-12-01 00:00:00

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    journal_title:Journal of hypertension

    pub_type: 杂志文章,随机对照试验


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    journal_title:Journal of hypertension

    pub_type: 杂志文章


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    journal_title:Journal of hypertension

    pub_type: 杂志文章


    authors: Izzo R,de Simone G,Devereux RB,Giudice R,De Marco M,Cimmino CS,Vasta A,De Luca N,Trimarco B

    更新日期:2011-04-01 00:00:00

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    journal_title:Journal of hypertension

    pub_type: 杂志文章


    authors: Sarzani R,Paci VM,Zingaretti CM,Pierleoni C,Cinti S,Cola G,Rappelli A,Dessì-Fulgheri P

    更新日期:1995-11-01 00:00:00

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    journal_title:Journal of hypertension

    pub_type: 杂志文章


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    更新日期:2016-08-01 00:00:00

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    pub_type: 杂志文章


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    更新日期:2009-06-01 00:00:00

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    pub_type: 临床试验,杂志文章,多中心研究


    authors: Raji A,Williams GH,Jeunemaitre X,Hopkins PN,Hunt SC,Hollenberg NK,Seely EW

    更新日期:2001-01-01 00:00:00

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    pub_type: 杂志文章


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    更新日期:2013-10-01 00:00:00