p2-73 the efficacy of estrogen on bradykinin receptor expression of rat offspring exposed to a...
TRANSCRIPT
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: [email protected]
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: [email protected]
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: [email protected]
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).