| Co-Investigator(Kenkyū-buntansha) |
KANAZAWA Masayuki Tohoku University, Graduate School of Medicine, Associate Professor, 大学院・医学系研究科, 助教授 (60282050)
MINAMI Naoyoshi Tohoku University Hospital, Lecturer, 病院・講師 (80333821)
ITO Osamu Tohoku University, Graduate School of Medicine, Research Associate, 大学院・医学系研究科, 助手 (00361072)
SATO Toshinobu Tohoku University Hospital, Associate Professor, 病院・助教授 (50312583)
TAKAGI Michiaki Yamagata University Hospital, Associate Professor, 医学部附属病院, 助教授 (40241707)
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| Budget Amount *help |
¥14,900,000 (Direct Cost: ¥14,900,000)
Fiscal Year 2005: ¥2,000,000 (Direct Cost: ¥2,000,000)
Fiscal Year 2004: ¥12,900,000 (Direct Cost: ¥12,900,000)
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| Research Abstract |
We assessed the effects of combination therapy with low-protein diet (LPD) and long-term exercise (EX). We also assessed the effects of a combination of these therapies and the angiotensin II receptor antagonist, olmesartan (OLS).
Methods : Male Wistar-Kyoto rats that were five-sixth-nephrectomized (NX) were divided into 6 groups ; 1) normal protein diet (18.3w% protein)(NPD) ; 2) NPD and EX with treadmill running (20m/min, 60min/day, 5days/week)(NPD+EX) ; 3) LPD (12.6w% protein) ; 4) LPD+EX ; 5) LPD+EX with 10mg/kg/day, OLS (LPD+EX+OLS) ; 6) Sham-operated (S), and the rats were then treated for 12weeks.
Results : The oxygen consumption (VO_2) when NX rats were running at a speed of 20m/min corresponded to about 80%, and the peak VO_2 in the NX rats was significantly decreased compared with that in the S group. LPD blunted rises in 24h-urinary excretion of protein (UP), reduced serum creatinine (Scr) and blood urea nitrogen (BUN), and improved index of glomerular sclerosis (IGS) and rela
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tive interstitial volume in the renal cortex (RIV). EX blocked the development of hypertension, reduced BUN, and improved IGS and RIV. UP in the LPD+EX, LPD+EX+OLS, S groups was significantly lower than that in the LPD. IGS and RIV in the LPD, LPD+EX, LPD+EX+OLS, S were significantly lower than those in the NPD+EX and LPD. Glomerular ED-1 positive cell in the LPD+EX, LPD+EX+OLS, S was significantly lower than that in the NPD. Systolic blood pressure (SBP) and RIV in the LPD+EX+OLS was significantly lower than those in the LPD+EX. EX enhanced capillarization as well as the proportion of type-I fiber in the soleus muscle.
Conclusions : These results indicate that LPD and EX have renoprotective effects, and suggest that the combination therapy with LPD and EX provides greater renoprotective effects than LPD alone. Moreover, simultaneous treatment of OLS and LPD+EX provides greater antihypertensive and renoprotective effects than treatment with LPD+EX, and EX had some additional effects without any complication in this rat model. Less
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