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 an d display cardiovascular dysfunction. When pregnant they develop mild hyper glycaemia. Diets high in saturated fat have been implicated in the developm ent of cardiovascular disease and vascular dysfunction. In the present stud y we have determined vascular function in small mesenteric arteries from of fspring of normal (OC) and diabetic (OD) rats fed standard chow and offspri ng of diabetic rats fed a diet high in saturated fats (OD-HF) from weaning to adulthood, and throughout their subsequent pregnancies. OD rats displaye d an increased sensitivity to noradrenaline (P < 0 . 05) and impaired sensi tivity to the endothelium-dependent vasodilator, acetylcholine. The compone nt of acetylcholine-induced relaxation attributable to endothelium-derived hyperpolarizing factor was reduced in OD-HF rats. Pregnant OD rats also dem onstrated impaired maximum relaxation to acetylcholine (pregnant OD rats v. pregnant OC rats P < 0 . 05). In pregnant OD-HF rats noradrenaline sensiti vity was enhanced and endothelium-dependent relaxation further reduced (pre gnant OD-HF rats v. pregnant OC rats P < 0 . 001). The isoprostane, 8-epi-p rostaglandin F-2 alpha, a marker of oxidative stress, was increased in preg nant OD rats (pregnant OD rats v. pregnant OC rats P < 0 . 001) and further increased in pregnant OD-HF rats (pregnant OD-HF rats v. pregnant OD rats P < 0 . 05). We conclude that a high-saturated-fat diet leads to deteriorat ion in specific components of vascular function in OD rats. When pregnant, vascular function of OD-HF rats is further compromised. Pregnancy in the OD rats is associated with a striking increase in a marker of oxidative stres s, which increases further if the saturated fat intake is raised.