Recent studies demonstrated that fructose intake can increase blood pressure in experimental animals. Oxidative stress has emerged as an important pathogenic factor in the development of hypertension. It has been reported that increased superoxide production in fructose-fed rat mediated through nicotinamide adenine dinucleotide phosphate NAD(P)H oxidase. Superoxide dismutase (SOD) is one of the most important enzymes against oxidative stress. However, the signaling mechanisms of fructose which induce hypertension through superoxide remain unclear. Nucleus tractus solitarii (NTS) is the integrative center for baroreflex. Our previous study had revealed that accumulation of superoxide in the NTS can induce hypertension. As an important antioxidant in red wine, resveratrol is likely to contribute to the potential of red wine to prevent cardiovascular disease. At pharmacological doses, resveratrol increases vascular nitric oxide (NO) levels and improves NO bioavailability in animal models. Resveratrol is a potent activator of AMPK in neuronal cell lines, primary neurons, and the brain. Recent reports have indicated that metformin targets AMPK which activates nNOS and eNOS. Therefore, we hypothesized that resveratrol causes blood pressure decrease through regulating nitric oxide and superoxide production in the NTS of fructose-fed rats. There were three specific aims: 1. To investigate whether fructose induce superoxide production and causes hypertension in the NTS. 2. To investigate which signaling pathway is involved in fructose-induced hypertension. 3. To investigate which signaling pathway is involved in resveratrol modulates blood pressure.
Male Wistar Kyoto rats (WKY) were divided into two groups: control group and fed with 10% fructose water group for 1 week. After one-week treatment, the systolic blood pressure and superoxide production increased significantly and the nitrate level in the NTS was significantly decreased. Immunoblotting showed that administration of fructose significantly increased NADPH oxidase subunits p22-phox, p67-phox activity, RAGE activity and reduce SOD2 activity in the NTS. Based on our previous studies, male Wistar-Kyoto rats (WKY) were divided into five groups: Group I: Control group; Group II: fructose-fed rats (FFR) fed with 10% fructose for 4 weeks; Group III: Control + resveratrol (R) rats received a gavage of resveratrol; Group IV: FFR+ resveratrol (FR) fed with 10% fructose and resveratrol ; Group V: FFR + 2weeks resveratrol (F2R) fed with 10% fructose and received a gavage of resveratrol 2 weeks. We found that systolic blood pressure measured by tail-cuff method in F group rats and F2R group rats revealed a significantly increased than C group rats continuously through week 0 to week 2 but R group rats and FR group rats were no difference with C group. However, received a gavage of resveratrol (10 mg/kg/d) 2 weeks, F2R group revealed a significantly decrease in SBP than the F group continuously through week 2 to week 4. Fructose-induced hypertension increased NADPH oxidase activity and SOD2 activity related to inhibit the production of NO in the regulation of blood pressure. These results suggest that in the NTS, intake of fructose induces NADPH oxidase activity and reduces SOD2 activity to increase blood pressure. Resveratrol can not only reverse fructose-induced hypertension but also prevent fructose-induced hypertension.
| Identifer | oai:union.ndltd.org:NSYSU/oai:NSYSU:etd-0823112-180106 |
| Date | 23 August 2012 |
| Creators | Su, Yu-ting |
| Contributors | Long-Sen Chang, Pei-Jung Lu, Pei-wen Cheng, Ching-Jiunn Tseng |
| Publisher | NSYSU |
| Source Sets | NSYSU Electronic Thesis and Dissertation Archive |
| Language | English |
| Detected Language | English |
| Type | text |
| Format | application/pdf |
| Source | http://etd.lib.nsysu.edu.tw/ETD-db/ETD-search/view_etd?URN=etd-0823112-180106 |
| Rights | user_define, Copyright information available at source archive |
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