Effects of overfeeding in breastfeeding period on blood pressure and vascular endothelial dilation function of rats

Abstract

Objective To study the effects of postnatal overfeeding and high-fat diet on blood pressure of rats, and to explore the pathophysiological mechanism underlying hypertension induced by continuous early postnatal overfeeding. Methods Male Sprague-Dawley rats were randomly divided into normal feeding group (10/litter) and overfeeding group (3/litter) on postnatal day 3 with a random number table. After weaning at postnatal week 3, the rats were randomly given standard chow or high-fat (HF) diet until week 16. Hence four groups were analyzed, namely normal feeding group, breastfed overfeeding group, post-weaning overfeeding group, and continuous overfeeding group. Body weight was continuously monitored in each week. Visceral fat pad(retroperitoneal and perigenital), systolic pressure, and heart rate were observed at week 3 and week 16. Thoracic aorta was sampled for measurement of vascular endothelial dilation function. Histological morphology was observed with HE staining, nitric oxide content of thoracic aorta was detected with nitrate reductase method. The mRNA expression of endothelial nitric oxide synthase (eNOS) in thoracic aorta was determined by real-time polymerase chain reaction. The protein expressions of eNOS and phosphorylated eNOS were determined by Western blot. Results At week 3, breastfed overfeeding rats displayed significantly larger body weight [(77.80±0.57) g vs. (62.80±0.85)g, t=14.576, P<0.01] and visceral fat [retroperitoneal: (8.19±0.49)mg/g vs. (4.92±0.31)mg/g, t=5.629, P<0.01; perigenital: (3.50±0.29)mg/g vs. (2.08±0.13)mg/g, t=4.552, P<0.01] compared with normal feedindg rats, and the protein expression of phosphorylated eNOS in aortic tissues was significantly reduced to week 16 (F=15.215, P<0.01); high-fat diet feeding after weaning further increased the body weight and fat mass in breastfed overfeeding rats. At week 16, continuous overfeeding rats showed hypertension [(149±1.94)mmHg (1 mmHg=0.133 kPa), F=22.834, P<0.01], impaired vascular endothelial dilation function (F=7.648, P<0.05), and reduced protein expression of phosphorylated eNOS(F=15.215, P<0.01), while the post-weaning overfeeding group only had elevated blood pressure. Conclusions Overfeeding in breastfeeding period and high-fat diet after weaning leads to hypertension. The continuous decrease in phosphorylated eNOS in vascular tissues may be an important molecular process participating in the occurrence of vascular endothelial dysfunction in adults induced by postnatal overfeeding. Key words: Early postnatal overfeeding; Vascular endothelial dilation function; Hypertension; Nitric oxide; Phosphorylated endothelial nitric oxide synthase