p2-73 the efficacy of estrogen on bradykinin receptor expression of rat offspring exposed to a...

Posters S149

P2-71 Early weight gain predicts cardiovascular responses to

stress in pre-pubertal children

A. Jones1,2 *, C. Osmond2, K.M. Godfrey2, D.I.W. Phillips2.1Department of Paediatric Cardiology, Great Ormond Street

Hospital, London, UK, 2MRC Epidemiology Resource Centre,

University of Southampton, UK

E-mail: aj@mrc.soton.ac.uk

Aims: Studies of adults suggest that poor early growth followed by

rapid weight gain later in childhood is predictive of hypertension.

Little data exists for children. We hypothesised that these

associations may result from differences in vascular resistance and

cardiac performance following stress.

Study design: Birth cohort.

Subjects: 68 boys and 72 girls (7 9 years old), born to mothers who

took part in an earlier study of fetal growth in Southampton, UK,

underwent the Trier Social Stress Test for Children (TSST-C) whilst

non-invasive cardiovascular measures were recorded.

Outcome measures: Blood pressure, thoracic impedance and

ECG were continuously recorded and used to derive indices of

systemic vascular resistance (SVRI), stroke volume (SV) and cardiac

output (CO).

Results: In boys, mean arterial pressure (MAP) and SVRI following

stress were highest in those who were small at birth, grew poorly in

infancy but had accelerated weight gain thereafter. Girls differed

in that early growth had no effect on MAP or SVRI. However, greater

postnatal growth correlated with SV, CO and MAP in both sexes.

Conclusions: These data suggest that there are independent and

contrasting effects of growth in different periods of early childhood

on SVRI, SV, and CO which are associated with greater arterial

pressure following stress. These differ by sex. We hypothesise

that differences in vascular and cardiac development related to

early growth may alter the dominant strategy (vascular or cardiac)

for the production of a hypertensive response to stress with

consequences for long-term cardiovascular health.

Weight gain Boys (N = 68) Girls (N = 72)

MAP SVRI SV CO MAP SVRI SV CO

Prenatal 0.62** 0.44* 0.04 0.21 0.08 0.07 0.08 0.00

0 11 months 0.29* 0.35* 0.43*** 0.38** 0.11 0.15 0.29* 0.26*

1 8 years 0.36* 0.33 0.32* 0.29 0.25* 0.28* 0.26* 0.28*

Correlation coefficients between cardiovascular parameters and weight gain

conditioned on prior growth periods. *P < 0.05. **P < 0.01. ***P < 0.001.

P2-72 Transfer of gangliosides across the human placenta

M.D. Mitchell1 *, K. Henare1, E. Lowe2, M. Naylor2, B. Fong2,

P. McJarrow2. 1Liggins Institute, University of Auckland and

National Research Centre for Growth and Development &2Fonterra Research Centre, Fonterra Cooperative Group Limited,

New Zealand

Background: Gangliosides are considered to have beneficial

effects on fetal neural development. Gangliosides are both

essential synaptical components as well as elicitors of neuronal

migration and neurite outgrowth. Definitive evidence of transfer of

gangliosides across the human placenta is, however, lacking.

Aims: To evaluate the transfer of a mixture of milk-derived

gangliosides across the human placenta.

Study design: We used the dual perfused human lobule for the

assessment of transfer of gangliosides. The ganglioside mixture was

purified from bovine milk and comprised mainly gangliosides GD3

and GM3. Perfusion was conducted for up to 3 hours using a closed

loop system.

Subjects: Experiments were conducted on lobules from six

placentae of uncomplicated term pregnancies.

Outcome measures: GM3 and GD3 contents of the perfusates were

measured by LC-MS using a Hypersil APS2 column, normal phase

acetonitrile gradient and detected in the LTQ orbitrap in negative

ion full scan.

Results: In all experiments there was evidence of transfer of GM3.

GM3 fetal perfusate concentrations increased approximately 6-fold

over time and by a significant amount over background. Maternal

perfusate GM3 concentrations were reduced on average by half

from approximately 300 ng/ml. For GD3 also there was evidence in

all cases of a significant reduction in maternal GD3 concentrations

averaging 25 30% but the concentrations in fetal perfusate were

below assay sensitivity.

Conclusions: Gangliosides transfer across the human placenta.

Although uptake of both GD3 and GM3 from the maternal perfusate

occurs, there appears to be a preference for GM3 uptake and

release into the fetal side.

P2-73 The efficacy of estrogen on bradykinin receptor

expression of rat offspring exposed to a maternal

low-protein diet

M. Miyakawa1 *, Y. Musha1, M. Ohtsuji2, S. Itoh1, S. Takeda1.1Department of Obstetrics and Gynecology, 2Department of

Pathology School of Medicine, Juntendo University, 2-1-1 Hongo,

Bunkyo-ku, Tokyo 113 8421, Japan

E-mail: mihomiya@med.juntendo.ac.jp

Aims: Our previous study showed that estrogen plays an important

role in limiting cardiovascular dysfunction, possibly via bradykinin

(BK)-mediated mechanisms. It is known that the expression of

BK2 and angiotensin II receptors is reduced in the kidneys of rats

under maternal protein restriction. Therefore, we hypothesized

that maternal malnutrition reduces expression of BK receptor

not only in kidneys but also in the cardiovascular system of

offspring. We also hypothesized that the reduction would be

worsened by oophorectomy and recovered by estrogen replacement

therapy (ERT).

Study design: Wistar rats were fed a diet containing either

18% casein (control group; C) or 9% casein (protein restriction

group; R) throughout pregnancy only. On day 50, the offspring

in each group were divided into three groups, which received

different operations: (a) sham group (CO, RO), an ovariectomized

group (CX, RX), and an ovariectomized + ERT group (CE,

RE). On d175, the mesenteric artery, aorta, kidney, and heart

were dissected, and the mRNA expression of BK2 receptor and

angiotensin II receptors (AT1, AT2) was examined by RT-PCR.

Results: The expression of BK2 receptors of the R groups was

significantly reduced in all organs. Especially in the heart,

BK receptors were significantly lower in RX than in RO, and were

recovered in the RE group.

Conclusions: ERT restored the expression of BK2 receptors in

estrogen-depleted rats. Our data suggested that gender differences

in cardiovascular dysfunction induced by maternal malnutrition

may be caused by suppressed renin angiotensin systems. Estrogen

might show the effects of the recovery of these changes through

regulation of BK receptor expression generally.

P2-74 Does initial infant feeding programme blood cholesterol

in adult life? A quantitative systematic review of the

evidence

C.G. Owen1 *, P.H. Whincup1, R.M. Martin2, G.D. Davey Smith2,

D.G. Cook1, for the EARLYREAD (Early Risk Exposures in Adult

Disease) Collaboration. 1Division of Community Health Sciences,

St George’s, University of London, UK, 2Department of Social

Medicine, University of Bristol, UK

E-mail: cowen@sgul.ac.uk

Aim: To examine whether breastfeeding is associated with lower

blood cholesterol levels in adult life, as suggested in some earlier

reports and our previous review.

Study design: Systematic review and meta-analysis including both

published and previously unpublished studies relating initial infant

feeding status to blood cholesterol levels in adulthood (>16 years).

Subjects: Data were available for 14 relevant studies (9287

breastfed, 4406 formula-fed).