(Circulation. 1998;98:2899-2904.)
© 1998 American Heart Association, Inc.
Basic Science Reports |
Offspring of Normal and Diabetic Rats Fed Saturated Fat in Pregnancy Demonstrate Vascular Dysfunction
From the Department of Endocrinology and Diabetes (E.K., C.L.) and the Fetal Health Research Group (P.G., L.P.), United Medical and Dental Schools, St. Thomas' Hospital, London, UK.
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Abstract |
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Background—Disturbances of the in utero environment may "program" for disease in later life. In this study, we determined whether dietary fat supplementation and/or diabetes in pregnancy can adversely affect vascular function in the offspring.
Methods and Results—Female Sprague-Dawley rats were fed a breeding diet or a diet high in saturated fat (30% wt/wt) for 10 days before mating, throughout pregnancy, and postpartum. Endothelium-dependent relaxation to acetylcholine was blunted in isolated femoral arteries of 15-day-old weanling pups from dams fed the 30%-fat diet. Endothelial dysfunction and enhanced constrictor responses to norepinephrine were also observed in an additional study of 60-day-old offspring of dams fed 20% saturated fat. Rats with streptozotocin-induced diabetes were also fed saturated fat during pregnancy. Femoral arteries from their 15-day-old offspring showed impairment of endothelium-dependent dilation and enhanced constrictor responses to norepinephrine and the thromboxane mimetic U46619 compared with young offspring of high-fat-fed normal dams. The 30%-fat diet was also deleterious to vascular function in the maternal diabetic animals when assessed in mesenteric arteries 16 days postpartum.
Conclusions—A high-fat diet in pregnancy led to vascular dysfunction in rat weanlings and young adult offspring. Vascular function further deteriorated in weanlings if the maternal rat was diabetic.
Key Words: nutrition • endothelium • pregnancy • arteries
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Introduction |
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Cardiovascular disease may have origins in fetal life. Retrospective population-based studies suggest that smaller size at birth or disproportionate growth is associated with increased incidence of hypertension and heart failure.1 Experimental studies in animals to investigate the proposed fetal "programming" of adulthood cardiovascular disease have therefore concentrated on the sequelae of maternal undernutrition,2 3 4 and little attention has been paid to possible in utero effects of a diet high in saturated fat, despite overwhelming evidence linking saturated fat intake to cardiovascular disease. Others have suggested that maternal diabetes may also have lasting adverse consequences on cardiovascular function of the next generation, particularly because offspring of diabetic pregnant rats demonstrate overt insulin resistance in adulthood.5 6
In this study, we determined the effect of a high-saturated-fat diet in pregnant rats on vascular function of isolated femoral arteries from 15-day-old and young adult offspring. In 15-day-old offspring, we also investigated the effect of maternal diabetes and the potential interaction between a high-saturated-fat diet and maternal diabetes.
Responses to constrictor agonists and to the endothelium-dependent vasodilator acetylcholine (ACh) were assessed in femoral arteries of the offspring by use of a small-vessel myograph. Mesenteric small arteries from the maternal circulation of control and diabetic animals were also investigated 16 days postpartum.
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Methods |
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Animals and Diets
Study 1: Vascular Function in Dams and 15-Day-Old Offspring
Female Sprague-Dawley rats (12 to 14 weeks old) were fed a standard breeding diet (4% fat, 22% protein, 51% carbohydrate, 5% fiber) or a diet high in saturated fat (30% lard, 18% protein, 40% carbohydrate, 3% fiber) for 10 days before mating, throughout pregnancy, and for 16 days postpartum. On day 1 to 2 of pregnancy, diabetes was induced in half the dams by caudal injection of streptozotocin (STZ; 30 mg/kg). Some control and diabetic rats fed the 30%-fat diet experienced difficulty in labor and were humanely killed. Diabetes was confirmed by demonstration of glycosuria (by Glucostix). Urinary glucose and ketones were monitored every 2 days during pregnancy by use of Glucostix and Ketostix, and to partially control diabetes, an insulin implant (one-half tablet; release rate 2 U/24 hours per implant for >40 days) was inserted subcutaneously after detection of ketonuria. Animals were weighed every 2 days until 20 to 21 days' gestation. At delivery, litter size was reduced to 5 to 6 pups. Vascular function was assessed in 15-day-old pups and in the dams at 16 days postpartum.
Study 2: Vascular Function in 60-Day-Old Offspring
Study 1 demonstrated abnormalities of vascular function in the
weanlings of normal dams fed the 30%-fat diet. A second study was
performed to determine whether this defect persisted into young
adulthood. Because 30%-fat-fed dams had experienced difficulty in
labor and a high neonatal mortality rate, the dietary fat intake was
reduced to 20% (wt/wt). After weaning, offspring were fed a diet of
standard rat chow (3% fat) until 60 days old, when vascular function
was assessed.
Evaluation of Vascular Function
Animals were killed by CO2 inhalation and
cervical dislocation. Blood samples were obtained by cardiac puncture,
and plasma was stored at –70°C before analysis. One pup from
each litter was studied. Third-order branches of the mesenteric artery
from the adult rat and the femoral artery from the offspring were
mounted as ring preparations on a small-vessel
myograph.7 Offspring mesenteric arteries were
found to be very friable, whereas femoral arteries demonstrated
reproducible viability. These were therefore used for the study.
Arteries failing to produce tension equivalent to a pressure of
100 mm Hg to 5 µmol/L norepinephrine (NE) in
KPSS (125 mmol/L KCl-substituted physiological
salt solution [PSS]) were rejected (a total of 5). Concentration
response curves were constructed to NE for maternal mesenteric arteries
(10-7 to 10-5 mol/L
increments at 2-minute intervals) and offspring femoral arteries
(10-8 to 10-5 mol/L). In
offspring arteries, a concentration response was also performed to the
thromboxane mimetic U46619 (10-10 to
10-6 mol/L). Arteries were then preconstricted
with NE to achieve 
80% maximum response and relaxation to ACh
assessed (10-9 to
10-5 mol/L). A similar protocol was followed to
evaluate relaxation to the NO donor spermine NONOate
(10-9 to 10-5 mol/L).
Blood Glucose, Fructosamine, and Lipids
Glucose concentrations were determined with a commercially
available assay based on an enzymatic (HK/G6P-DH) UV test.
Fructosamine, as an alternative estimate of glucose control, was
determined by use of a commercially available assay involving the
formation of formazan from nitro blue. Total plasma
cholesterol and triglyceride concentrations
were determined by assays based on the colorimetric
evaluation of enzyme activity (UNIMATE CHOL
[cholesterol oxidase] and UNIMATE TRIG [glycerol
phosphate dehydrogenase], respectively).
Chemicals
Chemicals used were NE (Sanofi Winthrop Ltd), ACh (Sigma
Chemical Co), and spermine NONOate (Alexis Corp). All chemicals for
PSS (in mmol/L: NaCl 119, NaHCO3 25,
D-glucose 5.5, KH2PO4 1.18,
MgSO4 7, H2O 1.17, KCl 4.7,
CaCl2 2.5, EDTA 0.026) were from BDH. STZ was
from Upjohn Co. Glucostix and Ketostix were from Boehringer
Mannheim. Insulin implants were from Linplant. Kits for estimation of
glucose, total cholesterol (UNIMATE CHOL), and
triglycerides (UNIMATE TRIG) were from Roche
Diagnostic Systems. High-saturated-fat and normal breeding
(No. 3 breeding diet) diets were from Special Diet Services.
Statistical Analysis
All values are given as mean±SEM. To account for small
differences in vessel diameter and in tension development, NE-induced
tension is expressed as percent of the maximum contractile response to
KPSS. Relaxation to ACh and spermine NONOate was expressed as a
percentage of NE-induced precontraction. The negative log of the
concentration (mol/L) of a drug required to produce 50% of the maximum
response (pEC50) was calculated after data were
fit to a sigmoidal curve (GraphPad Software Inc). Two arteries from
each animal were studied, and the mean pEC50 was
used in analysis. One-way ANOVA and Student's independent
t test were used for single comparisons, and the
Student-Newman-Keuls test was used for multiple comparisons between
groups of arteries. The Kruskal-Wallis nonparametric ANOVA
test was used for statistical comparisons of total
cholesterol and triglyceride levels (Instat;
GraphPad). Significance was assumed if P<0.05.
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Results |
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Study 1: Vascular Function in Dams and 15-Day-Old Offspring
Weight and Plasma Analyses
Maternal
Pregnancy-associated weight gain was significantly less in diabetic dams fed a high-fat diet than in nondiabetic dams fed the breeding diet (respective weight at 21-day gestation: 305.6±7.4 g, n=8 versus 386.4±8.9 g, n=10; P<0.001). Other weights during pregnancy were similar. Postpartum weights were similar to nonpregnant values in all groups. Mortality among the diabetic dams fed the 30%-fat diet was significantly greater than that among control dams fed the same diet (P<0.01), and pups (>5) survived from only 4 of the 8 litters delivered. Plasma glucose and fructosamine concentrations in the diabetic dams 16 days postpartum were significantly raised compared with control dams fed the breeding diet (diabetic versus control: glucose 26.4±2.3 mmol/L, n=9 versus 11.8±0.7 mmol/L, n=10, P<0.01; fructosamine 178±12 mmol/L, n=9 versus 125±7 mmol/L, n=10, P<0.01) and fed the 30%-fat diet (diabetic versus control: glucose 26.3±2.5 mmol/L, n=8 versus 12.8±1.3 mmol/L, n=10, P<0.01; fructosamine 193±23 mmol/L, n=8 versus 114±5 mmol/L, n=10, P<0.01). The raised plasma glucose concentrations in the control dams were equivalent to those we have previously reported when animals are killed by CO2 inhalation.8 Plasma triglyceride concentrations were significantly increased in the diabetic dams fed the 30%-fat diet (4.58±0.90 mmol/L, n=8 versus 1.27±0.25 mmol/L, n=10 for control dams on breeding diet; P<0.01) but not in any other group, whereas the total cholesterol concentration was significantly different only in the normal dams fed the 30%-fat diet, in which it was reduced (1.54±0.15 mmol/L, n=10 versus 1.90±0.09 mmol/L, n=10 for control dams on breeding diet; P<0.05).
Offspring (15 Days)
Offspring of the diabetic dams fed the 30%-fat diet were smaller
than offspring of normal dams fed the breeding diet (27.9±4.2 g, n=4
versus 39.6±1.0 g, n=10; P<0.001). All other young
offspring were of similar weights. Plasma glucose and
triglyceride concentrations were similar between the 4
groups, whereas total cholesterol concentrations were
significantly lower in offspring of control and diabetic rats fed the
30%-fat diet compared with control offspring of normal dams fed the
breeding diet (Table
).
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Vascular Function
There were no significant differences in internal artery diameter
among groups except between the mesenteric arteries of the nondiabetic
dams fed the high-fat diet and the control dams fed the breeding diet
(301±8 µm versus 337±7 µm, n=10;
P<0.05).
Constrictor Responses
Maternal (16 Days Postpartum).
maximal response to NE was increased in arteries from the
diabetic dams fed the 30%-fat diet compared with controls fed the
breeding diet (140.9±18.8% of contraction to KPSS, n=8 versus
99.7±5.3%, n=10; P<0.05). Neither diabetes alone nor the
30%-fat diet alone was associated with an abnormal maximal response to
NE (102.6±3.0%, n=9 and 94.2±2.7%, n=10, respectively). Sensitivity
to NE was similar among groups (pEC50:
control/breeding diet, 5.84±0.07 [n=10]; diabetic/breeding diet,
5.84±0.08 [n=9]; control/30%-fat diet, 5.74±0.05 [n=10];
diabetic/30%-fat diet, 5.90±0.08 [n=8]; Figure 1A).
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, Control dams fed breeding diet; 
,
diabetic dams fed breeding diet; 
, control dams fed high-fat diet;
and 
, diabetic dams fed high-fat diet. A, *P<0.05
maximum response to NE in diabetic dams fed high-fat diet vs diabetic
dams fed breeding diet. B, **P<0.01 maximum response in
offspring of diabetic dams fed high-fat diet vs offspring of control
dams fed breeding diet. When absent, error bars lie within
symbols.
Offspring (15 Days).
The maximal response to NE was increased in arteries from offspring of
diabetic dams fed the 30%-fat diet compared with offspring of the
control dams fed the breeding diet (122.1±14.4% of contraction to
KPSS, n=4 versus 83.3±3.2%, n=10; P<0.01). Neither
maternal diabetes alone nor a maternal high-fat diet alone was
associated with an abnormal maximal NE response in the offspring
(75.7±5.7%, n=8; 96.8±8.9%, n=8, respectively, P=NS
compared with offspring of controls fed the breeding diet; Figure 1B
),
nor was NE sensitivity different between groups
(pEC50: control/breeding diet, 6.10±0.11
[n=10]; diabetic/breeding diet, 6.46±0.13 [n=8]; control/30%-fat
diet, 5.89±0.08 [n=8]; diabetic/30%-fat diet, 6.26±0.14 [n=4];
Figure 1B). The maximal constrictor response to U46619 was also
increased in offspring of diabetic dams fed the 30%-fat diet
(148.3±23.3% of contraction to KPSS, n=4; P<0.001
compared with offspring of controls fed the breeding diet), but
sensitivity was unaffected (data not shown).
Endothelium-Dependent Relaxation
Maternal (16 Days Postpartum).
Maximal relaxation to ACh was impaired in the mesenteric arteries from
diabetic dams fed the 30%-fat diet compared with those of control dams
fed the breeding diet (79.6±4.9% of NE-induced contraction, n=8
versus 90.8±3.9%, n=10; P<0.01). Maximal ACh relaxation
was similar to controls in diabetic dams fed the breeding diet and
control dams fed the 30%-fat diet (94.3±1.9%, n=9 and 93.5±1.6%,
n=10, respectively), and sensitivity to ACh was similar between the 4
groups (pEC50: control/breeding diet, 7.04±0.10
[n=10]; diabetic/breeding diet, 7.00±0.10 [n=9]; control/30%-fat
diet, 7.08±0.08 [n=10]; diabetic/30%-fat diet, 7.08±0.19 [n=8];
Figure 2A).
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Offspring (15 Days).
Maximal relaxation to ACh was significantly reduced in the femoral
arteries from the offspring of normal dams fed a 30%-fat diet compared
with offspring of controls fed the breeding diet (76.5±3.6% of
NE-induced contraction, n=8 versus 85.0±3.4%, n=10;
P<0.01) and was further impaired if offspring were from
diabetic rats fed the 30%-fat diet (41.1±10.2%, n=4;
P<0.001). Maximal relaxation to ACh was normal in arteries
from offspring of diabetic animals on a breeding diet (85.4±4.5%,
n=8; Figure 2B). Arteries from offspring of diabetic dams fed the
30%-fat diet also showed decreased sensitivity to ACh compared with
those from offspring of controls fed the breeding diet
(pEC50: 6.45±0.2, n=4 versus 7.13±0.12, n=10;
P<0.01). Sensitivity to ACh was similar to controls in
arteries from offspring of normal animals fed the 30%-fat diet
(pEC50: 6.98±0.12, n=8) and from offspring of
diabetic animals fed the breeding diet (7.19±0.18, n=8; Figure 2B).
Endothelium-Independent Relaxation
Maximum relaxation to spermine NONOate was similar in
all groups of maternal rats, but sensitivity was significantly reduced
in the offspring of both controls and diabetic dams fed the 30%-fat
diet (pEC50: 5.39±0.07, n=8 and 5.29±0.15, n=4,
respectively) compared with offspring of control dams fed the breeding
diet (5.84±0.13, n=10; P<0.05 for both groups). Relaxation
was not different from controls in the offspring of diabetic dams
(pEC50: 5.80±0.13, n=9; Figure 3).
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Study 2: Vascular Function in 60-Day-Old Offspring
Weight and Plasma Analyses
None of the dams fed the 20%-fat diet had difficulty in
labor, and the size of the litters was not significantly different from
those of dams fed the breeding diet. However, mortality among the
neonates remained higher in the offspring of the rats fed the 20%-fat
diet (18.6% versus 5.3% for controls). Plasma
triglycerides were significantly raised in the 60-day-old
offspring of rats fed 20% fat compared with 60-day-old controls
(1.22±0.08 mmol/L, n=7 versus 0.92±0.11 mmol/L, n=7;
P<0.05). No significant differences were observed in any of
the other plasma analyses.
Vascular Function
Constrictor Responses
Sensitivity to NE was enhanced in arteries from the
60-day-old offspring of dams fed the 20%-fat diet compared with
offspring of dams fed the breeding diet (pEC50:
6.36±0.05, n=7 versus 5.92±0.13, n=7; P<0.05). Maximal
responses to NE were not significantly different from controls
(119.90±9.66% of contraction to KPSS, n=7 versus 95.55±6.33%, n=7;
Figure 4A). There were also no
significant differences in responses to U46619 between offspring of
dams fed 20% fat or of controls fed the breeding diet
(pEC50: 6.27±0.15, n=7 versus 6.08±0.07, n=7;
maximal response 110.66±8.98%, n=7 versus 99.25±17.90%, n=7).
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Endothelium-Dependent Relaxation
Arteries from the 60-day-old offspring of 20%-fat-fed dams
demonstrated decreased maximal relaxation to ACh (56.47±1.36% of
NE-induced preconstriction, n=7 versus 72.99±4.08%, n=7 for controls;
P<0.001), whereas sensitivity was similar to controls
(pEC50: 7.07±0.28, n=7 versus 7.19±0.19, n=7
for controls; Figure 4B).
Endothelium-Independent Relaxation
Relaxation to spermine NONOate was similar in 60-day-old
offspring of controls and 20%-fat-fed dams
(pEC50: 6.19±0.40, n=7 versus 6.08±0.39, n=7
for controls; maximum relaxation 55.63±5.40% of NE-induced
constriction, n=7 versus 59.00±6.01%, n=7 for controls; Figure 4C).
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Discussion |
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This study has shown that excessive saturated fat intake in pregnant rats can lead to disturbances of vascular function in weanlings and young adult offspring. This is a novel observation that provides support for the hypothesis that in utero events related to maternal nutrition may adversely affect specific pathways of vascular control and may predispose the offspring to vascular disease in later life.1
The femoral arteries of both young and older offspring of normal pregnant rats fed a diet enriched with lard showed poor endothelium-dependent relaxation. In the young weanlings, this was likely to be attributable in part to reduced vascular smooth muscle sensitivity to NO or to more rapid NO degradation, because the response to spermine NONOate was also blunted. Reduced relaxation to ACh and the NO donor in vitro provide evidence for abnormalities that, in vivo, could affect many aspects of normal vascular function. The enhanced sensitivity to NE in arteries from the young adults could also contribute to elevation of peripheral vascular resistance.
To the best of our knowledge, no study has previously directly investigated vascular function in the offspring of rats fed a high-saturated-fat diet, although raised blood pressure has been recorded9 in young adult offspring of dams fed a diet rich in coconut oil. Abnormal cholesterol metabolism has also been reported in the offspring of rats fed a diet rich in corn oil when the young animals were challenged with the same diet.10 In humans, the high incidence of fatty streaks in human fetal arteries and the correlation with maternal cholesterol also provides some evidence for the acquisition of vascular disease in utero.11
The origin of the vascular dysfunction induced in the offspring cannot be directly inferred from the present study. None of the plasma lipids measured were overtly raised in the 15-day-old offspring, but plasma triglycerides were elevated in the young adults. Hypertriglyceridemia may be indicative of insulin resistance, and triglycerides have been implicated in endothelial dysfunction.12 Hypercholesterolemia, frequently implicated in endothelial dysfunction, was not observed in the offspring; indeed, cholesterol was reduced in the weanlings. The low plasma cholesterol in the fat-fed dams agrees with previous studies in fat-fed normal rats13 and is characteristic of the rodent response to a saturated-fat diet. Free fatty acids could also play a role, because saturated fats interfere with the metabolism of fatty acids,14 some of which are precursors of vasoactive prostanoids.15
The poor reproductive performance in the dams fed the high-fat diet agrees with a similar study of fat-fed rats16 in which a 33% reduction in pregnancy rate and high pup mortality were observed. Fat-induced reproductive dysfunction is proposed to result from energetic inhibition of reproduction,17 inability of pups to metabolize the longer-chain fatty acids in the dams' milk,18 or maternal behavioral disorder, leading to cannibalism.19
Severe maternal diabetes together with high-fat feeding led to higher mortality among the pups. Those that survived were small but apparently healthy. However, the weanlings' femoral arteries were more responsive to NE. There was also deterioration of endothelium-dependent relaxation compared with offspring of nondiabetic dams fed the fat diet, whereas the response to the NO donor was similar. These offspring had acquired an endothelial defect similar to that observed in arteries of diabetic adult rats20 and in patients with diabetes.21 22 Because maternal diabetes per se was not associated with offspring vascular malfunction, the data imply that diabetes increased the susceptibility of the offspring vasculature to high maternal fat intake. We have reported both the abnormal transfer of certain free fatty acids across the isolated placenta in diabetic rats fed a 30%-saturated-fat diet23 and raised fetal blood glucose, the latter probably a reflection of fetal insulin resistance.24 The resultant fatty acid imbalance and/or fetal hyperglycemia potentially could lead to irreversible vascular dysfunction, maintained or "imprinted" in the vasculature of the newborn. The growth retardation in these offspring, sometimes observed in severe human diabetes, could also have contributed to cardiovascular dysfunction, because offspring of nutritionally deprived2 3 dams are reported to have raised blood pressure. Moreover, fetuses of severely diabetic dams are insulinopenic6 and may have lower insulin-like growth factor-1, both of which may lead to reduced growth and blunted NO synthesis.25 26
All offspring were suckled by their dams, and a contribution of the composition of the dam's milk to offspring vascular malfunction cannot be discounted. The abnormal nutrient composition, particularly of fatty acids, described in the milk of diabetic rats27 is likely to be further disturbed by a saturated fat diet. Additional studies in which offspring are cross-fostered with normal or diabetic dams would determine the relative importance of the suckling period compared with the influence of the in utero environment.
Diabetes was not associated with abnormal maternal vascular function, which contrasts with the endothelial dysfunction reported in previous studies in virgin diabetic animals28 and may reflect a pregnancy-induced "protection" against endothelial damage. However, when pregnant animals were fed the high-fat diet, vascular dysfunction was evoked in the maternal mesenteric arteries and was similar to that in the arteries of the offspring. Alone, this group of dams demonstrated an elevation of plasma triglycerides, which is also implicated in endothelial dysfunction.12
In conclusion, the data presented in this study suggest strongly that excessive maternal fat intake can play an important role in the development of cardiovascular disorders in the offspring and that maternal diabetes may present an additional confounding influence.
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Acknowledgments |
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The authors thank the trustees of St. Thomas' Hospital and Tommy's Campaign for financial support.
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Footnotes |
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Reprint requests to Professor Lucilla Poston, Division of Obstetrics and Gynaecology, United Medical and Dental Schools, St. Thomas' Hospital, London SE1 7EH, UK.
Received June 1, 1998; revision received August 10, 1998; accepted August 13, 1998.
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  K. Chechi, J. J. McGuire, and S. K. Cheema Developmental programming of lipid metabolism and aortic vascular function in C57BL/6 mice: a novel study suggesting an involvement of LDL-receptor Am J Physiol Regulatory Integrative Comp Physiol, April 1, 2009; 296(4): R1029 - R1040. [Abstract] [Full Text] [PDF]
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 W. Palinski Sodium Exposure Induces Stroke in a Genetically Susceptible Model: New Insights Into Early-Life Factors Modulating Adult Disease Circulation, March 24, 2009; 119(11): 1459 - 1462. [Full Text] [PDF]
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 D. Gniuli, A. Calcagno, M. E. Caristo, A. Mancuso, V. Macchi, G. Mingrone, and R. Vettor Effects of high-fat diet exposure during fetal life on type 2 diabetes development in the progeny J. Lipid Res., September 1, 2008; 49(9): 1936 - 1945. [Abstract] [Full Text] [PDF]
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 N. B. Ojeda, D. Grigore, and B. T. Alexander Developmental Programming of Hypertension: Insight From Animal Models of Nutritional Manipulation Hypertension, July 1, 2008; 52(1): 44 - 50. [Full Text] [PDF]
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M. M. Elahi, F. R. Cagampang, F. W. Anthony, N. Curzen, S. K. Ohri, and M. A. Hanson Statin Treatment in Hypercholesterolemic Pregnant Mice Reduces Cardiovascular Risk Factors in Their Offspring Hypertension, April 1, 2008; 51(4): 939 - 944. [Abstract] [Full Text] [PDF]
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 C. Gallou-Kabani, A. Vige, M.-S. Gross, C. Boileau, J.-P. Rabes, J. Fruchart-Najib, J.-P. Jais, and C. Junien Resistance to high-fat diet in the female progeny of obese mice fed a control diet during the periconceptual, gestation, and lactation periods Am J Physiol Endocrinol Metab, April 1, 2007; 292(4): E1095 - E1100. [Abstract] [Full Text] [PDF]
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 C. R. Gale, B. Jiang, S. M. Robinson, K. M. Godfrey, C. M. Law, and C. N. Martyn Maternal Diet During Pregnancy and Carotid Intima-Media Thickness in Children Arterioscler Thromb Vasc Biol, August 1, 2006; 26(8): 1877 - 1882. [Abstract] [Full Text] [PDF]
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 O. A. Khan, C. Torrens, D. E. Noakes, L. Poston, M. A. Hanson, L. R. Green, and S. K. Ohri Effects of pre-natal and early post-natal undernutrition on adult internal thoracic artery function Eur. J. Cardiothorac. Surg., December 1, 2005; 28(6): 811 - 815. [Abstract] [Full Text] [PDF]
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 O A Khan and C Shearman Is there a fetal origin of peripheral vascular disease? Heart, July 1, 2005; 91(7): 869 - 870. [Full Text] [PDF]
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R. B. Wichi, S. B. Souza, D. E. Casarini, M. Morris, M. L. Barreto-Chaves, and M. C. Irigoyen Increased blood pressure in the offspring of diabetic mothers Am J Physiol Regulatory Integrative Comp Physiol, May 1, 2005; 288(5): R1129 - R1133. [Abstract] [Full Text] [PDF]
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I. Khan, V. Dekou, M. Hanson, L. Poston, and P. Taylor Predictive Adaptive Responses to Maternal High-Fat Diet Prevent Endothelial Dysfunction but Not Hypertension in Adult Rat Offspring Circulation, August 31, 2004; 110(9): 1097 - 1102. [Abstract] [Full Text] [PDF]
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 S. M. Mone, M. W. Gillman, T. L. Miller, E. H. Herman, and S. E. Lipshultz Effects of Environmental Exposures on the Cardiovascular System: Prenatal Period Through Adolescence Pediatrics, April 1, 2004; 113(4/S1): 1058 - 1069. [Abstract] [Full Text] [PDF]
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 L. Gambling, S. Dunford, D. I Wallace, G. Zuur, N. Solanky, S K. S Srai, and H. J McArdle Iron deficiency during pregnancy affects postnatal blood pressure in the rat J. Physiol., October 15, 2003; 552(2): 603 - 610. [Abstract] [Full Text] [PDF]
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P. W Shaul Endothelial nitric oxide synthase, caveolae and the development of atherosclerosis J. Physiol., February 15, 2003; 547(1): 21 - 33. [Abstract] [Full Text] [PDF]
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I. Y. Khan, P. D. Taylor, V. Dekou, P. T. Seed, L. Lakasing, D. Graham, A. F. Dominiczak, M. A. Hanson, and L. Poston Gender-Linked Hypertension in Offspring of Lard-Fed Pregnant Rats Hypertension, January 1, 2003; 41(1): 168 - 175. [Abstract] [Full Text] [PDF]
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 A. E. Belevych, R. Beck, P. Tammaro, L. Poston, and S. V. Smirnov Developmental changes in the functional characteristics and expression of voltage-gated K+ channel currents in rat aortic myocytes Cardiovasc Res, April 1, 2002; 54(1): 152 - 161. [Abstract] [Full Text] [PDF]
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 C. E Bertram and M. A Hanson Animal models and programming of the metabolic syndrome: Type 2 diabetes Br. Med. Bull., November 1, 2001; 60(1): 103 - 121. [Abstract] [Full Text] [PDF]
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P Ghosh, D Bitsanis, K Ghebremeskel, M A Crawford, and L Poston Abnormal aortic fatty acid composition and small artery function in offspring of rats fed a high fat diet in pregnancy J. Physiol., June 15, 2001; 533(3): 815 - 822. [Abstract] [Full Text] [PDF]
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T Ozaki, H Nishina, M A Hanson, and L Poston Dietary restriction in pregnant rats causes gender-related hypertension and vascular dysfunction in offspring J. Physiol., January 1, 2001; 530(1): 141 - 152. [Abstract] [Full Text] [PDF]
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R. T Gerber, K. Holemans, I. O'Brien-Coker, A. I Mallet, R. van Bree, F A. Van Assche, and L. Poston Cholesterol-independent endothelial dysfunction in virgin and pregnant rats fed a diet high in saturated fat J. Physiol., June 1, 1999; 517(2): 607 - 616. [Abstract] [Full Text] [PDF]
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