Raised saturated-fat intake worsens vascular function in virgin and pregnant offspring of streptozotocin-diabetic rats.

Adult offspring of severely diabetic pregnant rats are insulin resistant and display cardiovascular dysfunction. When pregnant they develop mild hyperglycaemia. Diets high in saturated fat have been implicated in the development of cardiovascular disease and vascular dysfunction. In the present study we have determined vascular function in small mesenteric arteries from offspring of normal (OC) and diabetic (OD) rats fed standard chow and offspring of diabetic rats fed a diet high in saturated fats (OD-HF) from weaning to adulthood, and throughout their subsequent pregnancies. OD rats displayed an increased sensitivity to noradrenaline (P < 0.05) and impaired sensitivity to the endothelium-dependent vasodilator, acetylcholine. The component of acetylcholine-induced relaxation attributable to endothelium-derived hyperpolarizing factor was reduced in OD-HF rats. Pregnant OD rats also demonstrated impaired maximum relaxation to acetylcholine (pregnant OD rats v. pregnant OC rats P < 0.05). In pregnant OD-HF rats noradrenaline sensitivity was enhanced and endothelium-dependent relaxation further reduced (pregnant OD-HF rats v. pregnant OC rats P < 0.001). The isoprostane, 8-epi-prostaglandin F2alpha, a marker of oxidative stress, was increased in pregnant OD rats (pregnant OD rats v. pregnant OC rats P