Wu Kay L H, Wu Chih-Wei, Tain You-Lin, Chao Yung-Mei, Hung Chun-Ying, Tsai Pei-Chia, Wang Wei-Sing, Shih Cheng-Dean
Institute for Translational Research in Biomedicine, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung, 83301, Taiwan, Republic of China; Department of Senior Citizen Services, National Tainan Institute of Nursing, Tainan 700, Taiwan, Republic of China.
Institute for Translational Research in Biomedicine, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung, 83301, Taiwan, Republic of China.
J Nutr Biochem. 2017 Mar;41:73-83. doi: 10.1016/j.jnutbio.2016.11.013. Epub 2016 Dec 5.
Both genetic and dietary factors determine the development of hypertension. Whether dietary factor impacts the development of hereditary hypertension is unknown. Here, we evaluated the effect of daily high-fructose diet (HFD) on the development of hypertension in adolescent spontaneously hypertensive rats (SHR). Six-week-old SHR were randomly divided into two groups to receive HFD or normal diet (ND) for 3 weeks. The temporal profile of systolic blood pressure, alongside the sympathetic vasomotor activity, in the SHR-HFD showed significantly greater increases at 9-12 weeks of age compared with the age-matched SHR-ND group. Immunofluorescence was used to identify the distribution of reactive oxygen species (ROS), oxidants and antioxidants in rostral ventrolateral medulla (RVLM) where sympathetic premotor neurons reside. In RVLM of SHR-HFD, the levels of ROS accumulation and lipid peroxidation were elevated. The changes in protein expression were measured by Western blot. NADPH oxidase subunit gp91 and angiotensin II type I receptor were up-regulated in RVLM neuron. On the other hand, the expression of extracellular superoxide dismutase was suppressed. Both molecular and hemodynamic changes in the SHR-HFD were rescued by oral pioglitazone treatment from weeks 7 to 9. Furthermore, central infusion with tempol, a ROS scavenger, effectively ameliorated ROS accumulation in RVLM and diminished the heightened pressor response and enhanced sympathetic activity in the SHR-HFD. Together, these results suggest that HFD intake at adolescent SHR may impact the development of hypertension via increasing oxidative stress in RVLM which could be effectively attenuated by pioglitazone treatment.
遗传因素和饮食因素都决定了高血压的发展。饮食因素是否会影响遗传性高血压的发展尚不清楚。在此，我们评估了每日高果糖饮食（HFD）对青春期自发性高血压大鼠（SHR）高血压发展的影响。将六周龄的SHR随机分为两组，分别给予HFD或正常饮食（ND），持续3周。与年龄匹配的SHR-ND组相比，SHR-HFD组在9至12周龄时收缩压的时间变化以及交感神经血管运动活动显著增加。采用免疫荧光法确定活性氧（ROS）、氧化剂和抗氧化剂在交感神经运动前神经元所在的延髓头端腹外侧区（RVLM）的分布。在SHR-HFD组的RVLM中，ROS积累和脂质过氧化水平升高。通过蛋白质印迹法检测蛋白质表达变化。RVLM神经元中NADPH氧化酶亚基gp91和血管紧张素II 1型受体上调。另一方面，细胞外超氧化物歧化酶的表达受到抑制。从第7周开始用吡格列酮口服治疗可挽救SHR-HFD组的分子和血流动力学变化。此外，向中枢注射ROS清除剂tempol可有效改善RVLM中的ROS积累，并减轻SHR-HFD组增强的升压反应和增强的交感神经活动。总之，这些结果表明，青春期SHR摄入HFD可能通过增加RVLM中的氧化应激来影响高血压的发展，而吡格列酮治疗可有效减轻这种影响。
