Offspring of normal and diabetic rats fed saturated fat in pregnancy demonstrate vascular dysfunction.

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.