Predictive adaptive responses to maternal high-fat diet prevent endothelial dysfunction but not hypertension in adult rat offspring.

BACKGROUND: Population-based studies suggest that fetal adaptive responses to maternal dietary imbalance confer survival benefit when the postnatal diet remains suboptimal but increase susceptibility to cardiovascular disease when postnatal nutrition is improved. We have investigated "predictive adaptive" responses in a rodent model in which adult offspring of fat-fed dams develop characteristics of the metabolic syndrome. METHODS AND RESULTS: Sprague-Dawley rats were fed a fat-rich diet or normal chow throughout pregnancy and weaning. Vascular endothelial function and blood pressure were determined in 180-day-old offspring of fat-fed dams raised on standard chow (FC) or on the fat-rich diet (FF) and in offspring of chow-fed dams raised on chow (CON). Small mesenteric artery endothelium-dependent dilation to acetylcholine was impaired in male and female FC (by ANOVA, P<0.001 versus CON) but similar to CON in FF (P=NS). Blood glucose was lower in FF versus FC. Heart rate was reduced in male FC versus CON (P<0.05) but not in FF. Plasma triglyceride concentrations were reduced in male FF compared with CON (P<0.05). Blood pressure was raised in female FC (systolic, 132.5+/-3.0 mm Hg versus CON, 119.0+/-3.8 mm Hg, P<0.05; diastolic, 91.2+/-1.7 mm Hg versus CON, 81.1+/-1.4 mm Hg, P<0.05) and in female FF (systolic, 132.5+/-4.2 mm Hg versus CON, P<0.05; diastolic, 91.0+/-1.9 mm Hg versus CON, P<0.05). Blood pressure was similar to CON in male FC and FF. CONCLUSIONS: Predictive adaptive responses prevent endothelial dysfunction and reduced heart rate in offspring of fat-fed dams if offspring are raised on the same diet but do not prevent development of raised blood pressure.

Developmental programming of aortic and renal structure in offspring of rats fed fat-rich diets in pregnancy.

Evidence from human and animal studies suggests that maternal nutrition can induce developmental programming of adult hypertension in offspring. We have previously described a model of maternal dietary imbalance in Sprague-Dawley rats whereby administration of a maternal diet rich in animal lard programmes the development of increased blood pressure, insulin resistance, dyslipidaemia, obesity and mesenteric artery endothelial dysfunction in adult offspring. To further characterize the mechanism of hypertension in this model we have examined vascular and renal structure in adult offspring of Sprague-Dawley rats fed a control diet (OC) or lard-rich diet (OHF) during pregnancy and suckling followed by a control diet post-weaning. To gain further insight, we assessed aortic reactivity and elasticity in an organ bath preparation and renal renin and Na+,K+-ATPase activity. Plasma aldosterone concentration was also measured. Stereological examination of the aorta in OHF demonstrated reduced endothelial cell volume and smooth muscle cell number compared with OC. Adult OHF animals showed increased aortic stiffness and reduced endothelium-dependent relaxation. Renal stereology showed no differences in kidney weight, glomerular number or volume in OHF compared with OC, but renin and Na+,K+-ATPase activity were significantly reduced in OHF compared with controls. Programmed alterations to aortic structure and function are consistent with previous observations that exposure to maternal high fat diets produces systemic vascular changes in the offspring. Despite normal renal stereology, altered renal Na+,K+-ATPase and renin activity offers further insight into the mechanism underlying the increased blood pressure characteristic of this model.

Gender-linked hypertension in offspring of lard-fed pregnant rats.

Epidemiological studies suggest an association between maternal nutrition and offspring cardiovascular disease. We previously demonstrated endothelial dysfunction and abnormal aortic fatty acid composition in adult female offspring of rats fed animal lard during pregnancy. We have now further investigated this model. Female Sprague-Dawley rats were fed a control breeding diet (5.3% fat) or a diet rich in lard (25.7% fat) 10 days before and throughout pregnancy and lactation. Male and female offspring were implanted with radiotelemeters for recording of blood pressure, heart rate, and activity at 80, 180, and 360 days of age. Reactivity to acetylcholine and to nitric oxide were assessed in isolated small mesenteric arteries from 80- and 180-day-old littermates. Systolic blood pressure (awake phase) was raised in female offspring (180 days: offspring of control, 130.7+/-1.6 mm Hg, n=5, versus offspring of lard-fed, 138.1+/-2.9, n=5, P=0.029; 360 days: offspring of control, 129.7+/-3.7 mm Hg, n=6, versus offspring of lard-fed, 142.1+/-3.2, n=6, P=0.005). Diastolic blood pressure was also raised at 180 days (offspring of control, 87.6+/-1.0 mm Hg, n=5, versus offspring of lard-fed, 94.7+/-2.6, n=5, P=0.011). Blood pressure was not raised in male offspring. Endothelium-dependent relaxation to acetylcholine was blunted in male and female offspring of lard-fed dams (80 and 180 days). Feeding a diet rich in lard to pregnant rats leads to gender-related cardiovascular dysfunction in normally fed offspring.