Intrauterine undernutrition: expression and activity of the endothelial nitric oxide synthase in male and female adult offspring

Abstract

Our data show that intrauterine undernutrition: (1) induces hypertension both in the male and female offspring, hypertension being more severe in male than in female rats; (2) alters endothelium-dependent responses in aortas from the resulting offspring. The endothelial dysfunction is associated with a decrease in activity/expression of eNOS in aortas from male offspring. The mechanism involved in altered response to ACh in female offspring might be a consequence of reduction in estrogen levels leading to reduced eNOS activity.

Maternal Diet During Pregnancy and Carotid Intima–Media Thickness in Children

“…Rats exposed during gestation to maternal energy-or proteinrestricted diets have an increased incidence of endothelial dysfunction and hypertension. [5][6][7][8] Similar outcomes have been observed in the offspring of rats fed a high-fat diet during pregnancy. 9,10 Whether there is any relation in humans between characteristics of maternal diet during pregnancy and atherogenesis is not known, although the observation that maternal hypercholesterolemia during pregnancy is linked with faster progression of early atherosclerotic lesions in children suggests that the type and quantity of fat in the maternal diet may play a role in fetal atherogenesis.…”

“…Studies in animals have shown impaired endothelial function-a marker of propensity to atherosclerosis 24 -in offspring of rats fed a calorie-restricted diet during pregnancy. 7,8 The association between lower maternal energy intake in pregnancy and increased IMT in the child was partly accounted for by a tendency for the children of mothers with lower intakes to be heavier at age 9 years, although energy intake remained an independent predictor after adjustment for this. The association was not explained by maternal prepregnancy BMI or whether a mother underwent strenuous exercise during pregnancy, although children whose mothers underwent no such exercise in late gestation had a slightly greater mean IMT.…”

Sex differences in the fetal programming of hypertension

“…LBW in human is associated with vascular dysfunction (51), an observation supported by animal models of fetal programming (16,26,52,53). Thus, fetal programming contributes to both structural and physiological changes in the vasculature which may contribute to increased risk for development of CVD associated with LBW.…”

“…Although decreased acetylcholine-induced relaxation is observed in both male and female offspring from nutrient restricted dams, vascular abnormalities are more pronounced in males than in females (26,52,53). Endothelial nitric oxide synthase activity, but not gene expression of eNOS, is reduced in female offspring from undernourished dams (52). Estrogen levels are reduced in these female offspring suggesting that the vasoprotective role of the estrogen on the vascular responses is lost in females subjected to fetal undernutrition.…”

Predictive Adaptive Responses to Maternal High-Fat Diet Prevent Endothelial Dysfunction but Not Hypertension in Adult Rat Offspring

“…3 Developmental programming of cardiovascular and metabolic risk factors is readily observable in animal models of nutrient restriction. Rodents exposed in early development to maternal protein deprivation 4 -6 or maternal global dietary restriction [7][8][9][10] demonstrate insulin resistance and hypertension in adulthood when maintained on a balanced diet. Developmental programming of adulthood cardiovascular and metabolic disorders in animals is, however, not limited to dietary restriction, because we and others have shown that exposure to a maternal diet rich in saturated fat [11][12][13][14] or cholesterol 15 also results in features of the metabolic syndrome, vascular dysfunction, and vascular atherogenic lesions in adult animals raised on standard chow.…”