Effects of high fructose intake on the development of hypertension in the spontaneously hypertensive rats: the role of AT1R/gp91PHOX signaling in the rostral ventrolateral medulla

• Published in: The Journal of nutritional biochemistry 2017-03, Vol.41, p.73-83
• Main Authors: 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
• Format: Article
• Language: English
• Subjects: High-fructose diet; Hypertension; Oxidative stress; Rostral ventrolateral medulla; Spontaneously hypertensive rat
• ISSN: 0955-2863; 1873-4847
• DOI: 10.1016/j.jnutbio.2016.11.013

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 gp91phox 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. [Display omitted]