Effects Of Postnatal Overfeeding On Vascular Endothelial Function And Blood Pressure

Hypertension is a risk factor for cardiovascular disease, with high blood pressure as the main clinical manifestations. The incidence of hypertension increases year by year, and shows a trend of younger age. High blood pressure in childhood commonly leads to hypertension in adulthood. Further investigations show that younger age trend of hypertension is closely associated with obesity. It has been demonstrated that vascular endothelial diastolic dysfunction plays an important role in the development of obesity induced-hypertension, which involves decreased generation or activity of endothelial nitric oxide (NO).Early overnutrion is the risk factor for children and adolescents obesity which lead to adulthood obesity, but the effects of early postnatal overnutrition on blood pressure and vascular endothelial diastolic function are not clear. In this study, we observed the effects of early postnatal overfeeding and postweaning high fat diet on blood pressure and vascular endothelial function. Our study might provide a new idea and practical molecular target on the prevention and treatment for cardiovascular disease in adulthood.ObjectiveTo study the effects of neonatal overfeeding and postweaning high fat diet on body weight, fat weight, blood lipid, serum letipn, blood pressure, vascular structure and endothelial function of rats. Aim to clarify the role of early postnatal overfeeding on hypertension. Methods1. Animal model:male Sprague-Dawley rats were divided into litter sizes of three (small litters, SL) or ten (normal litters, NL) on postnatal day3and then given either a control or a high fat (HF) diet from postnatal week3(W3) to week16(W16). Four groups were analyzed, namely NL, SL, NL-HF and SL-HF. All indexes were observated at W3and W16.2. Body weight was continuously monitored. Blood pressure and heart rat were recorded at W3,W6and W16. Fat pad (epididymal and retroperitonea) weight, blood lipid and serum letipn were recorded at W3and W16.3. Vascular endothelial function of thoracic aorta was analyzed.4. Histological analyses and NO content of thoracic aorta were recorded. The mRNA expressions of endothelial nitric oxide synthase (eNOS) in thoracic aorta were determined by real-time qPCR. The protein expression of eNOS and P-eNOS were determined by western-blot.Results1. At W3, SL rats displayed heavier body weight and visceral fat pad compared with NL rats, and this effect persisted to W16. Body weights in SL-HF rats were persistently higher than that in all other three groups, while NL-HF rats showed greater body weight than NL rats until W9. SL rats displayed higher serum letipn compared with NL rats at W3and persisted to W16, but SL-HF group showed the highest level. No matter whether exposed to NL or SL, post-weaning HF diet increased the levels of serum total cholesyerol(TC), triglyceride (TG) and low density lipoprotein cholesterin (LDL), while serum high density lipoprotein cholesterin (HDL) of SL-HF group was below NL-HF and NL groups at W16.2. Blood pressure and vascular endothelial diastolic function showed no significant difference between SL and NL group at W3. Blood pressure showed no significant difference among groups at W6. At W16, SL-HF group appeared the highest blood pressure and impaired vascular endothelium, while NL-HF group only appeared higher blood pressure.3. At W16, the levels of aortas NO in SL-HF group were obviously lower than that in NL and NL-HF group, but did not differ significantly from SL group.4. The protein expression of P-eNOS in SL rats was lower than that in NL rats at W3, an effect that persisted into W16. At W16, despite the HF diet resulted in decreased protein expression of P-eNOS compared with NL group, there was no difference between SL and NL-HF group, and SL-HF rats showed the lowest expression. In addition, mRNA expression and protein expression of eNOS showed no difference between groups at W3and W16.ConclusionEarly postnatal overfeeding promotes early onset and the sustainability of obesity and leptin resistance in rats, which beome more seriously on a high-fat diet after weaning. Under high-fat diet after weaning, postnatal overfeeding aggravates hypertension and leads to the occurrence of vascular endothelial dysfunction. Postnatal overfeeding in rats induced continuously decrease in P-eNOS of thoracic aorta, a process might participate in the occurrence of vascular endothelial dysfunction.