title: Effects of high fructose intake on the development of hypertension in the spontaneously hypertensive rats: the role of AT1R/gp91PHOXsignaling in the rostral ventrolateral medulla.
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 gp91phoxand 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.
authors.affiliation: 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. Electronic address: klhwu@adm.cgmh.org.tw.
authors.forename: Kay L H
authors.initials: KL
authors.lastname: Wu
authors.affiliation: Institute for Translational Research in Biomedicine, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung, 83301, Taiwan, Republic of China.
authors.forename: Chih-Wei
authors.initials: CW
authors.lastname: Wu
authors.affiliation: Institute for Translational Research in Biomedicine, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung, 83301, Taiwan, Republic of China; Department of Pediatrics, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University, College of Medicine, Kaohsiung 833, Taiwan, Republic of China.
authors.forename: You-Lin
authors.initials: YL
authors.lastname: Tain
authors.affiliation: Institute for Translational Research in Biomedicine, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung, 83301, Taiwan, Republic of China.
authors.forename: Yung-Mei
authors.initials: YM
authors.lastname: Chao
authors.affiliation: Institute for Translational Research in Biomedicine, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung, 83301, Taiwan, Republic of China.
authors.forename: Chun-Ying
authors.initials: CY
authors.lastname: Hung
authors.affiliation: Institute for Translational Research in Biomedicine, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung, 83301, Taiwan, Republic of China.
authors.forename: Pei-Chia
authors.initials: PC
authors.lastname: Tsai
authors.affiliation: Institute for Translational Research in Biomedicine, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung, 83301, Taiwan, Republic of China.
authors.forename: Wei-Sing
authors.initials: WS
authors.lastname: Wang
authors.affiliation: Department of Pharmacy, Graduate Institute of Pharmaceutical Technology, Tajen University, Pingtung County 90741, Taiwan, Republic of China. Electronic address: cdshih@mail.tajen.edu.tw.
authors.forename: Cheng-Dean
authors.initials: CD
authors.lastname: Shih
mesh_terms: D000818:Animals; D000959:Antihypertensive Agents / Q000627:therapeutic use; D000070601:Diet, Carbohydrate Loading / Q000009:adverse effects*; D005632:Fructose / Q000009:adverse effects*; D006973:Hypertension / Q000209:etiology* / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control; D007004:Hypoglycemic Agents / Q000627:therapeutic use; D015227:Lipid Peroxidation / Q000187:drug effects; D008297:Male; D008526:Medulla Oblongata / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D000074662:NADPH Oxidase 2 / Q000737:chemistry / Q000378:metabolism*; D009419:Nerve Tissue Proteins / Q000819:agonists / Q000378:metabolism; D009474:Neurons / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D018384:Oxidative Stress / Q000187:drug effects; D000077205:Pioglitazone; D011897:Random Allocation; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D017382:Reactive Oxygen Species / Q000378:metabolism; D044140:Receptor, Angiotensin, Type 1 / Q000819:agonists / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects; D045162:Thiazolidinediones / Q000627:therapeutic use
chemical_list: D000959:Antihypertensive Agents; D007004:Hypoglycemic Agents; D009419:Nerve Tissue Proteins; D017382:Reactive Oxygen Species; D044140:Receptor, Angiotensin, Type 1; D045162:Thiazolidinediones; D005632:Fructose; C500593:Cybb protein, rat; D000074662:NADPH Oxidase 2; D000077205:Pioglitazone
keywords: High-fructose diet; Hypertension; Oxidative stress; Rostral ventrolateral medulla; Spontaneously hypertensive rat