Uterine artery function in pregnant rats fed a diet supplemented with animal lard.
We hypothesised that maternal uterine artery vascular dysfunction could contribute to cardiovascular dysfunction in offspring of rats fed a diet rich in fat. Sprague-Dawley rats were fed for 10 days prior to pregnancy and throughout gestation either: (a) a control breeding diet, or (b) the same diet supplemented with 20 % w/w lard, vitamins, essential micronutrients and protein to control values. At 20 days gestation vascular function was assessed in uterine arteries and third-order mesenteric arteries. Vascular reactivity in response to application of potassium, noradrenaline, the thromboxane analogue U46619, acetylcholine and nitric oxide was assessed. Maternal plasma concentrations of factors likely to contribute to endothelial dysfunction were measured. Maximum acetylcholine-induced relaxation was impaired in the mesenteric arteries of the lard-fed dams (max % relaxation: lard-fed, 69.7 +/- 6.48; control, 85.37 +/- 2.69, P = 0.03). Uterine artery vascular function was similar in the two groups (max % acetylcholine-induced relaxation: lard-fed, 73.7 +/- 4.01; control, 77.5 +/- 4.72, P = 0.98). Concentrations of plasma lipids, 8-epi-PGF(2alpha) and leptin were normal, whereas insulin and corticosterone concentrations were raised in the lard-fed group (insulin (ng ml(-1)): lard-fed, 8.04 +/- 0.47; control, 1.35 +/- 0.37, P < 0.0001; corticosterone (ng ml(-1)): lard-fed, 1164.0 +/- 170.9; control, 541.9 +/- 96.3, P = 0.005). Fetal and placental weights were reduced in lard-fed dams (fetus (g): lard-fed, 4.27 +/- 0.38; control, 2.96 +/- 0.40, P = 0.025; placenta (g): lard-fed, 0.72 +/- 0.06; control, 0.57 +/- 0.04, P = 0.05). Cardiovascular dysfunction in offspring is not associated with reduced uterine artery endothelial function but is associated with activation of the hypothalamic-pituitary-adrenal axis, hyperinsulinaemia and fetoplacental growth retardation.
Taylor
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Maternal and Fetal Research Unit, GKT Department of Women's Health, King's College London, UK. paul.taylor@kcl.ac.uk
Khan
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Lakasing
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Dekou
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O'Brien-Coker
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Mallet
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Hanson
M A
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Poston
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D000821:Animal Feed; D000818:Animals; D001158:Arteries / Q000502:physiology; D001835:Body Weight / Q000187:drug effects; D002784:Cholesterol / Q000097:blood; D003345:Corticosterone / Q000097:blood; D004032:Diet; D004041:Dietary Fats / Q000494:pharmacology*; D015237:Dinoprost / Q000031:analogs & derivatives*; D004435:Eating / Q000187:drug effects; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000502:physiology*; D004734:Energy Metabolism / Q000187:drug effects; D028441:F2-Isoprostanes / Q000097:blood; D005260:Female; D007328:Insulin / Q000097:blood; D020738:Leptin / Q000097:blood; D015227:Lipid Peroxidation / Q000187:drug effects; D008098:Litter Size / Q000187:drug effects; D008638:Mesenteric Arteries / Q000502:physiology; D011247:Pregnancy; D051381:Rats; D017207:Rats, Sprague-Dawley; D012098:Reproduction / Q000187:drug effects; D014599:Uterus / Q000098:blood supply*; D014661:Vasoconstriction / Q000502:physiology; D014664:Vasodilation / Q000502:physiology
D004041:Dietary Fats; D028441:F2-Isoprostanes; D007328:Insulin; D020738:Leptin; C075750:8-epi-prostaglandin F2alpha; D002784:Cholesterol; D015237:Dinoprost; C029310:lard; D003345:Corticosterone