Abstract P116: Effects of Febuxostat on Blood Pressure and Renal Functions in Dahl Salt-Sensitive Rats

Several clinical and basic studies have reported that febuxostat (Fx), xanthine oxidase (XO) inhibitor, has anti-hypertensive and renal protective effects. However, these effects of Fx are controversial, and the mechanisms have not been clarified. In this study, we investigated the effects of Fx on blood pressure and renal functions in Dahl salt-sensitive rats. Eight-week-old, male Dahl salt-sensitive rats were divided into three groups: 1) normal salt diet (NS) group; 2) high salt diet (HS) group; 3) HS + Fx group. The NS or HS groups were fed diet containing 0.6% or 8% NaCl, and the Fx group treated with Fx (3 mg/kg/day in drinking water). After 8 weeks, the systolic blood pressure (SBP), renal functions, and renal histology were examined. HS significantly increased the SBP, urinary protein excretion, and plasma creatinine and uric acid (p<0.01), and exacerbated glomerular sclerosis. HS also significantly increased urinary H2O2 and XO activity in the renal cortex (3.27±0.37 vs. 0.78±0.16 mU/mg protein) and outer medulla (1.84±0.15 vs. 0.76±0.04 mU/mg protein) (p<0.01). The Fx treatment significantly ameliorated the HS-increased SBP (174±6 vs. 209±4 mmHg), urinary protein excretion (152±21 vs. 325±40 mg/day), plasma creatinine (0.29±0.01 vs. 0.41±0.03 mg/dl), uric acid (0.53±0.06 vs. 1.67±0.21 mg/dl) (p<0.01) and glomerular sclerosis. The Fx treatment significantly suppressed the HS-increased urinary H2O2 (339.6±27.8 vs. 483.8±47.4 nM/day, p<0.01), and almost completely inhibited XO activity in the renal cortex and outer medulla. In additional study, we investigated the effects of Fx on blood pressure and renal functions in spontaneously hypertensive rats. The Fx treatment (3 mg/kg/day in drinking water) for 8 weeks did not significantly change the SBP (189±6 vs. 205±4 mmHg), plasma creatinine (0.19±0.01 vs. 0.18±0.01 mg/dl), or urinary albumin excretion (214±20 vs. 206±33 μg/day). These results indicate that anti-hypertensive and renal protective effects of Fx in Dahl salt-sensitive rats fed high-salt diet, suggesting that Fx has anti-hypertensive and renal protective effects in salt-sensitive hypertension.