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 |
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| Institution: | 1. Institute for Translational Research in Biomedicine, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung, 83301, Taiwan, Republic of China;2. Department of Senior Citizen Services, National Tainan Institute of Nursing, Tainan 700, Taiwan, Republic of China;3. Department of Pediatrics, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University, College of Medicine, Kaohsiung 833, Taiwan, Republic of China;4. Department of Pharmacy, Graduate Institute of Pharmaceutical Technology, Tajen University, Pingtung County 90741, Taiwan, Republic of China;1. Department of Orthopaedic Surgery, University of Missouri;2. University of Alabama at Birmingham, School of Medicine;3. Division of Orthopaedic Surgery, University of Alabama at Birmingham;4. Center for Surgical Medical Acute Care Research and Transitions, Birmingham Veterans Affairs Medical Center;5. Department of Surgery, University of Alabama at Birmingham;1. 70 Lien Hai RD, Department of Business Management, National Sun Yat-sen University, Kaohsiung 80424, Taiwan;2. 700 University RD Department of Finance, National University of Kaohsiung, Kaohsiung 81148, Taiwan;3. 415 Chien Kung RD, Department of Wealth and Taxation Management, National Kaohsiung University of Applied Sciences, Kaohsiung 80778, Taiwan |
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| Abstract: | 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. |
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