Central and peripheral contributions to obesity-associated hypertension: impact of early overnourishment.

Obesity induced by a high-fat diet was associated with increased tail-cuff blood pressure in adult rats. The mechanisms underlying obesity-related hypertension are unclear, but increased sympathetic activation most probably plays a role. Neuroendocrine alterations observed in obesity may influence both feeding patterns and blood pressure. Work from our laboratory has shown that chronic overfeeding in rats leads to changes in neuropeptide Y (NPY) and alpha-melanocyte stimulating hormone (alphaMSH) in the hypothalamus. These peptides have central effects on blood pressure, indicating that obesity-related changes in the CNS may impact on cardiovascular function. Population studies suggest that nutrition in early life can influence the subsequent risk of obesity and high blood pressure. To examine the impact of early postnatal overnutrition on blood pressure and adipose-derived mediators, we adjusted rat litters to 3 or 12 pups (overnutrition and control, respectively). Pups raised in small litters were 15% heavier at weaning, and this intervention was associated with a modest elevation of blood pressure and body weight as adults (16 weeks). Animals raised in small litters had increased 11beta-hydroxysteroid dehydrogenase type 1 (11beta-HSD1) mRNA in white adipose tissue as adults, which may impact on cardiovascular function. Adjustment of diet after weaning, to 30% fat diet or standard chow, allowed comparison of the impact of different periods of overnourishment. Implementation of a high-fat diet at weaning overcame the effect of litter size on body weight from 10 weeks of age. Blood pressure rose progressively with high-fat feeding and was positively correlated with leptin and body weight. Chronic consumption of a high-fat diet led to marked increases in leptin and insulin and modest increases in blood pressure, and impacts on brain transmitters implicated in the regulation of both appetite and blood pressure. Overnourishment during early postnatal development led to profound changes in body weight at weaning, which tended to abate with maturation. It also led to long-term changes in some adipose-derived mediators, possibly increasing cardiovascular risk.