Maternal High Fat‐High Sucrose Diet is Associated with Elevated Offspring Hypothalamic Oxidative Stress and Blood Pressure Responses to Psychological Stress.

There is mounting evidence that diets high in fat and sucrose (HFS) during pregnancy adversely affect offspring cardiovascular health. The aims of the present study were to assess the level of oxidative stress (OS) in brainstem cardiovascular control sites and compare blood pressure (BP) responses to psychological stress in HFS and control offspring. Dams were fed a HFS diet (21% fat, 34% sucrose; control, 4.8% fat, 0% sucrose) from 4 weeks prior to mating until weaning. Three‐month old male offspring (n=7) were assessed for levels of the antioxidant glutathione and the OS marker protein carbonyl (PCs) in brainstem cardiovascular nuclei. At 9–12 months, cardiovascular variables were acquired from both males (control n=5; HFS=6) and females (control n=4; HFS=3) at rest and in response to mild (air jet, AJ) and moderate (restraint, RS) psychological stress using telemetry. Male rats were perfused and brains were processed immunohistochemically for Fos protein expression. Data are expressed as mean ± SE, statistical significance was taken as p<0.05. HFS offspring exhibited increased retroperitoneal adiposity as a percentage of wet weight (2% vs 3.7%). Markers of OS were elevated in the hypothalamus, comprising a two‐fold increase in PCs and 40% reduction in glutathione. No significant differences were observed in the medulla or midbrain of programmed offspring. Resting mean blood pressure (BP) was higher in both male and female HFS offspring than controls (male; 102.0±3.0 vs 94.2±2.6 mmHg, female; 104.4±3.7 vs 93.1±2.9 mmHg). BP responses to psychological stress were also enhanced. In HFS males, both stressors elicited greater initial increases in systolic BP (AJ; +30±3.3 vs +17±2.1 mmHg, RS; +39±1.9 vs +26±2.8 mmHg), while recovery was slower in AJ only (45 min post‐AJ, +13±1.6 vs +3±2.4 mmHg from baseline). A larger increase in blood pressure variability (low frequency component) was also observed in HFS males during both stressors, while no difference in heart rate or heart rate variability was observed between groups. In HFS females, the initial systolic BP response to RS was greater (+41.3±1.9 vs 33.3±0.9 mmHg), however, there was no difference in AJ (HFS, 25.0±2.3 vs 24.3±4.3 mmHg). In contrast to males, recovery was similar to controls in HFS females. HFS offspring also showed reduced Fos expression in the midbrain periaqueductal grey (PAG) in response to stress. Following AJ, the number of Fos‐positive neurons was reduced by ~40% in the lateral and ventrolateral PAG, while post‐RS a decrease in Fos expression was observed in the dorsomedial (70% reduction), dorsolateral (43%) and lateral (47%) PAG. No difference in Fos expression was observed in the hypothalamus. The results suggest that maternal HFS elicits increased OS in the hypothalamus of offspring and programs a pro‐hypertensive phenotype characterised by exaggerated cardiovascular responses to psychological stress.