14 Effects of Maternal Gestational Diabetes on Vascular Reactivity in Adult Rat Female Offspring.

Abstract

Background: Exposure to diabetes in utero produces an adverse environment for the fetus and is a significant risk factor for the development of metabolic syndrome (obesity, glucose intolerance and hypertension). Previous studies have found that offspring of rats rendered diabetic throughout pregnancy demonstrate vascular dysfunction. The effects of the development of diabetes later in pregnancy (gestational onset diabetes) on vascular function in the offspring are not known. Hypothesis: Female offspring of mother rats made diabetic during the latter half of pregnancy demonstrate altered vascular reactivity and endothelial dysfunction. Methods: Pregnant rats were made diabetic by administration of streptozotocin (50 mg/kg ip) on day 12 of gestation. Insulin was administered subcutaneously twice each day to maintain glucose levels of 100 - 400 mg/dl and avoid ketoacidosis. Control rats received injections of saline. All rat pups were cross-fostered after birth to non-diabetic dams. Offspring (n = 7, each group) were sacrificed at 6-8 mo of age and aortic vascular reactivity assessed by wire myography. Data were assessed by ANOVA. Results: Birthweights and postnatal growth were similar between the offspring of control and diabetic dams. Endothelium-intact aortas from offspring of diabetic rats showed significantly (p < 0.05) enhanced contractility to KCl, endothelin-1 and noradrenaline, but not angiotensin II or serotonin. Co-administration of L-NNA (a nitric oxide synthase inhibitor) normalized the responses to endothelin-1 and noradrenaline. Relaxation to acetylcholine (endothelium dependent) but not nitroprusside (endothelium independent) was also significantly impaired in offspring of diabetic rats. Conclusions: Adult offspring of gestational diabetic rats displayed altered vascular responses and endothelial dysfunction. Alterations in endothelial function may provide a mechanistic link between intrauterine exposure to diabetes and the later development of cardiovascular disease.