p1-41 developmental programming of cardiovascular dysfunction by maternal obesity

1
S94 Posters P1-40 The influence of birth weight on blood pressure and body composition of Brazilian children from 5 to 8 years of age J.A. Pereira, P.H.C. Rond´ o*, J.M.P. Souza, J.O. Lemos, J.F. Moura, R.S.C. Dias. Department of Nutrition, School of Public Health, University of S˜ ao Paulo. Avenida Dr. Arnaldo 715, CEP- 01246 904, ao Paulo, SP, Brazil E-mail: [email protected] Aim: To assess the relationship between birth weight (BW), blood pressure and body composition of children. Study design: Prospective cohort study. Subjects: 472 Brazilian children from 5 to 8 years of age. Outcome measures: Systolic and diastolic blood pressure, mid-upper arm circumference, waist circumference, skinfold thickness. Results: Linear regression models were applied to investigate the relationship between independent (BW and birth length BL) and dependent (weight, height, BMI, waist circumference WC, fat mid-upper arm area FMUAA, systolic blood pressure SBP and diastolic blood pressure DBP, cholesterol, triglycerides) variables. The prevalence of children with a SBP the 95 centile was high (35.16%); 5.09% of the children had a DBP the 95 centile. BW was positively correlated with FMUAA and BMI (p < 0.001). In the linear regression model, adjusted for BMI, it was noticed a significant inverse relationship between BW and SBP. There were no statistically significant associations between BL and systolic and diastolic blood pressures. Conclusions: The inverse relationship between BW with actual SBP and the high prevalence of overweight, justify the control of the nutritional status of children since the fetal period and the monitoring of BP in the pediatric routine. P1-41 Developmental programming of cardiovascular dysfunction by maternal obesity A.M. Samuelsson*, A.I. Awopetu, P.A. Matthews, P.D. Taylor, L. Poston. Division of Reproduction and Endocrinology, King’s College London, United Kingdom E-mail: [email protected] Aims: To study the effects of maternal diet-induced obesity on offspring cardiovascular function in a murine model. Study design: Female C57BL/6J mice were fed either a control diet (4% corn oil) or a highly palatable, hypercalorific diet (20% fat, 38% sugar) for six weeks and throughout pregnancy and lactation. All offspring were weaned onto control diet and cardiovascular function was assessed at three and six months of age by remote radio-telemetry. Surgical implantation of a radio-telemetry probe via the left carotid artery was performed in anesthetized mice using medetomidine and ketamine, and reversed by atipamezole. Outcome measures: Systolic and diastolic blood pressure and heart rate were recorded in conscious freely moving mice over a 24 hour period, one week after surgery. Results: Both male and female offspring of obese dams (OO) showed a significant increase in systolic blood pressure and heart rate compared to controls (OC) at three months (P < 0.05), which was further augmented at six months (average night- time systolic blood pressure [mmHg] at six months, mean±SEM, male OO, 134±1.4 vs. OC, 124.4±2.1, n = 8, P< 0.05; female OO, 136.8±2.4 vs OC, 121.8±4.2, n = 8, P< 0.01; average night- heart rate [bpm] at six months, male OO, 636.6±15.8 vs OC, 549.5±21.6, n = 8, P< 0.01; female OO, 632.7±21.1 vs OC, 554.5±24.8, n = 8, P< 0.01). Conclusions: Maternal diet-induced obesity programmes systolic hypertension and increased heart rate in male and female offspring from early adulthood contributing to increased risk of metabolic syndrome and cardiovascular disease in this model. Funded by the British Heart Foundation and EARNEST. P1-42 Placental restriction leads to an upregulation of the angiotensin II receptors AT 1 R and AT 2 R mRNA in the aorta of the fetal sheep in late gestation A.D. Snell 1,2 *, I.C. McMillen 1 , S. Gentili 1 , J.L. Morrison 1 . 1 Early Origins of Adult Health Research Group, Sansom Institute, University of South Australia, Adelaide, South Australia 5005, Australia, 2 School of Molecular and Biomedical Science, Discipline of Physiology, The University of Adelaide, 5005, Australia E-mail: [email protected] Aims: Chronic hypoxia, which can be induced by placental restriction (PR), leads to a redistribution of blood flow from the periphery to vital organs like the brain. Whilst studies have implicated the actions of Angiotensin II (Ang II), in the regulation of peripheral vasoconstriction, it is unknown whether there is an upregulation of the Angiotensin Type 1 receptor (AT 1 R) which mediates the vasoconstrictor actions of Ang II. Therefore the aim of the current study was to determine the impact of PR on the expression of AT 1 R and AT 2 R mRNA in the aorta of the sheep fetus in late gestation. Study design: Carunclectomy was performed in 6 non-pregnant ewes to induce PR. Vascular catheters were inserted in 6 PR and 4 control (C) fetuses at 103 117d. Post mortem was performed at 139 141d and gene expression was measured using normalized Real-time PCR. Outcome measures: Fetal Weight, mean gestational PO 2 and relative expression of AT 1 R and AT 2 R. Results: Fetal weight (C, 4.3±0.3 kg; PR, 2.5±0.3 kg) and mean gestational PO 2 (C, 20.6±1.9; PR, 2.7±0.8 mmHg) were significantly lower in PR fetuses (P < 0.01). In the aorta, the relative expression of AT 1 R (C, 0.03±0.003; PR, 0.05±0.005) and AT 2 R (C, 0.006±0.002; PR, 0.016±0.002) were each higher in PR fetuses (P < 0.05). Conclusions: Previous studies have shown that the PR fetus is more dependent on Ang II for blood pressure maintenance. Increased expression of AT 1 R and AT 2 R in the aorta may be an indicator of global upregulation of the Ang II receptors under low oxygen conditions. P1-43 The influence of birthweight on cardiomyocyte number in postnatal lambs V. Stacy 1 *, M. Probyn 2 , R. De Matteo 1 , N. Wreford 1 , R. Harding 1 , M.J. Black 1 . 1 Department of Anatomy and Cell Biology, Monash University, VIC 3800, Australia, 2 School of Biomedical Sciences, University of Queensland, Brisbane, QLD, Australia E-mail: [email protected] Aims: Little is known about the effects of IUGR on the development of cardiomyocytes. As cardiomyocytes cease proliferating soon after birth, the ultimate number is determined during fetal and early postnatal life. Twinning provides a natural model of moderate IUGR. Our aim was to determine whether IUGR due to twinning alters cardiac muscle development in sheep. Methods: Hearts were collected at necropsy from either singleton (n = 5) or twin (n = 5) lambs at 9 weeks of age. At this age, cardiomyocytes in sheep are terminally differentiated. The walls of the left and right ventricles were systematically sampled. The number of cardiomyocytes was estimated using an unbiased optical disector/fractionator stereological technique. Results: At birth, twins were 17% lighter than singletons ( p = 0.007) and remained lighter to 9 weeks. At 9 weeks the hearts of twins were 28% lighter than those of singletons ( p< 0.001) but were not different when adjusted for body weight. At 9 weeks, although there was no significant difference between twins and singletons in total ventricular cardiomyocyte number (i.e. in left ventricle, septum and right ventricle), there was a significant positive relationship between the number of cardiomyocytes and body weight at birth ( p = 0.002) and at 9 weeks ( p = 0.002). Conclusions: Our study shows that low birthweight leads to smaller hearts with reduced numbers of ventricular cardiomyocytes. A reduced number of cardiomyocytes could lead to compromised

Upload: am-samuelsson

Post on 17-Sep-2016

212 views

Category:

Documents


0 download

TRANSCRIPT

Page 1: P1-41 Developmental programming of cardiovascular dysfunction by maternal obesity

S94 Posters

P1-40 The influence of birth weight on blood pressure and

body composition of Brazilian children from 5 to 8 years

of age

J.A. Pereira, P.H.C. Rondo *, J.M.P. Souza, J.O. Lemos, J.F. Moura,

R.S.C. Dias. Department of Nutrition, School of Public Health,

University of Sao Paulo. Avenida Dr. Arnaldo 715, CEP- 01246 904,

Sao Paulo, SP, Brazil

E-mail: [email protected]

Aim: To assess the relationship between birth weight (BW), blood

pressure and body composition of children.

Study design: Prospective cohort study.

Subjects: 472 Brazilian children from 5 to 8 years of age.

Outcome measures: Systolic and diastolic blood pressure,

mid-upper arm circumference, waist circumference, skinfold

thickness.

Results: Linear regression models were applied to investigate the

relationship between independent (BW and birth length BL) and

dependent (weight, height, BMI, waist circumference WC, fat

mid-upper arm area FMUAA, systolic blood pressure SBP and

diastolic blood pressure DBP, cholesterol, triglycerides) variables.

The prevalence of children with a SBP � the 95 centile was

high (35.16%); 5.09% of the children had a DBP � the 95 centile.

BW was positively correlated with FMUAA and BMI (p < 0.001). In

the linear regression model, adjusted for BMI, it was noticed a

significant inverse relationship between BW and SBP. There were

no statistically significant associations between BL and systolic and

diastolic blood pressures.

Conclusions: The inverse relationship between BW with actual

SBP and the high prevalence of overweight, justify the control of

the nutritional status of children since the fetal period and the

monitoring of BP in the pediatric routine.

P1-41 Developmental programming of cardiovascular

dysfunction by maternal obesity

A.M. Samuelsson*, A.I. Awopetu, P.A. Matthews, P.D. Taylor,

L. Poston. Division of Reproduction and Endocrinology, King’s

College London, United Kingdom

E-mail: [email protected]

Aims: To study the effects of maternal diet-induced obesity on

offspring cardiovascular function in a murine model.

Study design: Female C57BL/6J mice were fed either a control diet

(4% corn oil) or a highly palatable, hypercalorific diet (20% fat,

38% sugar) for six weeks and throughout pregnancy and lactation.

All offspring were weaned onto control diet and cardiovascular

function was assessed at three and six months of age by remote

radio-telemetry. Surgical implantation of a radio-telemetry probe

via the left carotid artery was performed in anesthetized mice using

medetomidine and ketamine, and reversed by atipamezole.

Outcome measures: Systolic and diastolic blood pressure and heart

rate were recorded in conscious freely moving mice over a 24 hour

period, one week after surgery.

Results: Both male and female offspring of obese dams (OO)

showed a significant increase in systolic blood pressure and

heart rate compared to controls (OC) at three months (P< 0.05),

which was further augmented at six months (average night-

time systolic blood pressure [mmHg] at six months, mean±SEM,

male OO, 134±1.4 vs. OC, 124.4±2.1, n = 8, P < 0.05; female

OO, 136.8±2.4 vs OC, 121.8±4.2, n = 8, P < 0.01; average night-

heart rate [bpm] at six months, male OO, 636.6±15.8 vs

OC, 549.5±21.6, n = 8, P < 0.01; female OO, 632.7±21.1 vs

OC, 554.5±24.8, n = 8, P < 0.01).

Conclusions: Maternal diet-induced obesity programmes systolic

hypertension and increased heart rate in male and female offspring

from early adulthood contributing to increased risk of metabolic

syndrome and cardiovascular disease in this model.

Funded by the British Heart Foundation and EARNEST.

P1-42 Placental restriction leads to an upregulation of the

angiotensin II receptors AT1R and AT2R mRNA in the

aorta of the fetal sheep in late gestation

A.D. Snell1,2 *, I.C. McMillen1, S. Gentili1, J.L. Morrison1. 1Early

Origins of Adult Health Research Group, Sansom Institute,

University of South Australia, Adelaide, South Australia 5005,

Australia, 2School of Molecular and Biomedical Science, Discipline

of Physiology, The University of Adelaide, 5005, Australia

E-mail: [email protected]

Aims: Chronic hypoxia, which can be induced by placental

restriction (PR), leads to a redistribution of blood flow from

the periphery to vital organs like the brain. Whilst studies have

implicated the actions of Angiotensin II (Ang II), in the regulation

of peripheral vasoconstriction, it is unknown whether there is

an upregulation of the Angiotensin Type 1 receptor (AT1R) which

mediates the vasoconstrictor actions of Ang II. Therefore the aim

of the current study was to determine the impact of PR on the

expression of AT1R and AT2R mRNA in the aorta of the sheep fetus

in late gestation.

Study design: Carunclectomy was performed in 6 non-pregnant

ewes to induce PR. Vascular catheters were inserted in 6 PR and

4 control (C) fetuses at 103 117d. Post mortem was performed

at 139 141d and gene expression was measured using normalized

Real-time PCR.

Outcome measures: Fetal Weight, mean gestational PO2 and

relative expression of AT1R and AT2R.

Results: Fetal weight (C, 4.3±0.3 kg; PR, 2.5±0.3 kg) and

mean gestational PO2 (C, 20.6±1.9; PR, 2.7±0.8 mmHg) were

significantly lower in PR fetuses (P< 0.01). In the aorta, the relative

expression of AT1R (C, 0.03±0.003; PR, 0.05±0.005) and AT2R

(C, 0.006±0.002; PR, 0.016±0.002) were each higher in PR fetuses

(P< 0.05).

Conclusions: Previous studies have shown that the PR fetus is more

dependent on Ang II for blood pressure maintenance. Increased

expression of AT1R and AT2R in the aorta may be an indicator

of global upregulation of the Ang II receptors under low oxygen

conditions.

P1-43 The influence of birthweight on cardiomyocyte number

in postnatal lambs

V. Stacy1 *, M. Probyn2, R. De Matteo1, N. Wreford1, R. Harding1,

M.J. Black1. 1Department of Anatomy and Cell Biology, Monash

University, VIC 3800, Australia, 2School of Biomedical Sciences,

University of Queensland, Brisbane, QLD, Australia

E-mail: [email protected]

Aims: Little is known about the effects of IUGR on the development

of cardiomyocytes. As cardiomyocytes cease proliferating soon

after birth, the ultimate number is determined during fetal and

early postnatal life. Twinning provides a natural model of moderate

IUGR. Our aim was to determine whether IUGR due to twinning

alters cardiac muscle development in sheep.

Methods: Hearts were collected at necropsy from either singleton

(n = 5) or twin (n = 5) lambs at 9 weeks of age. At this age,

cardiomyocytes in sheep are terminally differentiated. The walls

of the left and right ventricles were systematically sampled. The

number of cardiomyocytes was estimated using an unbiased optical

disector/fractionator stereological technique.

Results: At birth, twins were 17% lighter than singletons ( p = 0.007)

and remained lighter to 9 weeks. At 9 weeks the hearts of

twins were 28% lighter than those of singletons ( p < 0.001) but

were not different when adjusted for body weight. At 9 weeks,

although there was no significant difference between twins and

singletons in total ventricular cardiomyocyte number (i.e. in left

ventricle, septum and right ventricle), there was a significant

positive relationship between the number of cardiomyocytes and

body weight at birth ( p = 0.002) and at 9 weeks ( p = 0.002).

Conclusions: Our study shows that low birthweight leads to smaller

hearts with reduced numbers of ventricular cardiomyocytes. A

reduced number of cardiomyocytes could lead to compromised