Abstract P150: Chronic Exercise Provides Antihypertensive Effects With Upregulation of Oxidative Stress-Induced Nitric Oxide Upregulation in The Kidney of High-Fructose Fed Rat

Abstract

Object: The fructose consumption was reported to correlated with increase of oxidative stress, which thereby impair nitric oxide system. Chronic exercise (Ex) can provide antihypertensive effects though nitric oxide upregulation. The mechanisms of Ex in nitric oxide upregulation are various and remains unclarified. Method: A total of 24 Sprague Dawley rats at 5-week age were allocated to 3 groups as controlled diet group (CON), high-fructose diet group (HFr) and HFr underwent 12-week chronic exercise (HFr-Ex). The systolic blood pressure (SBP) and urinary albumin excretion were taken every 2 weeks. At the final week, after the insulin tolerance test, the rats were euthanized. The plasma and kidneys were obtained. The plasma and renal oxidative stress markers were measured. The nitric oxide related parameters including renal endothelial nitric oxide synthase (eNOS) expression were measured. Result: The SBP was significantly increased in HFr than CON, which Ex significantly attenuated the SBP elevation (115 vs. 141 mmHg, p<0.01). Ex reversed albuminuria induced by HFr without alteration in creatinine clearance ratio (474 vs. 1446μg/day, p<0.01). Ex significantly lowered uric acid, and attenuated the insulin resistance (uric acid, 1.41 vs. 2.05 mg/dL, p<0.01; HOMA-IR, 0.64 vs. 0.50, p<0.01). Ex significantly inhibited renal cortex xanthine oxidase activity (XO), meanwhile the NADPH oxidase activity (NADPH) was even enhanced (XO, 15.7 vs. 11.8 units/mg protein, p<0.05; NADPH, 897 vs. 1370 c.p.m, p<0.01). The hydrogen peroxide was not changed. Renal eNOS expression was increased in HFr (228%, p<0.01), and Ex significantly enhanced the expression higher than HFr (316%, p<0.01). The phosphorylation of eNOS in serine 1177 were inhibited by HFr and reversed by Ex (87%, p<0.01). AMPK was not changed by HFr, and Ex significantly increased AMPK expression (266%, p<0.01). The phosphorylation of AMPK at threonine 172 were increased by HFr (306%, p<0.01), and Ex even enhanced the expression (473%, p<0.01). Conclusion: Ex provided antihypertensive effects with nitric oxide upregulation. The mechanism of nitric oxide upregulation may mediate with the improve of phosphorylation and alteration in oxidases activities.