Combination of chronic exercise and antihypertensive therapy enhances renoprotective effects in rats with renal ablation.
BACKGROUND
We assessed the renal protective effects of treatment with moderate exercise (EX), with EX plus olmesartan (OLS), with EX plus azelnidipine (AZN), and with the three together in a rat model of chronic renal failure (CRF).


METHODS
Male 5/6-nephrectomized Wistar Kyoto (WKY) rats were divided into six groups according to the following treatments for: (i) no EX (C); (ii) moderate EX with treadmill running (20 m/min for 60 min/day, 5 days/week) (EX); (iii) EX+OLS (10 mg/kg/day); (iv) EX+AZN (3 mg/kg/day); (v) EX+OLS (5 mg/kg/day)+AZN (1.5 mg/kg/day); and (vi) sham operation (S). The rats were then treated for 12 weeks.


RESULTS
EX, EX+OLS, EX+AZN, and EX+OLS+AZN showed decreases in the serum creatinine (Scr), an index of glomerular sclerosis (IGS), the relative interstitial volume of the renal cortex (RIV), the number of ED-1 (monoclonal antibody) positive cells (ED1(+)) and the glomerular expression score of alpha-smooth muscle actin (alpha-SMA(+)). EX+OLS, EX+AZN, and EX+OLS+AZN blocked the development of hypertension, increased the number of Wilms' tumor-1 (WT-1) positive cells (WT1(+)); EX+OLS and EX+OLS+AZN blunted the increases in proteinuria. In particular, blood urea nitrogen (BUN), ED1(+), alpha-SMA(+), WT1(+), IGS, and RIV in the EX+OLS+AZN were the lowest among all the nephrectomized groups.


CONCLUSIONS
In the results, simultaneous treatment of EX, OLS, and AZN showed renal protective effects in this rat model suggesting that the treatment may affect the macrophage infiltration to the glomerulus, the fibroblast accumulation in the glomerulus, the mesangial activation, and the podocyte differentiation.
Lu
Hongmei
H
Department of Internal Medicine and Rehabilitation Science, Tohoku University Graduate School of Medicine, Sendai, Japan.
Kanazawa
Masayuki
M
Ishida
Atsuko
A
Tufescu
Andreia
A
Sasaki
Yuko
Y
Ito
Osamu
O
Kurosawa
Hajime
H
Sato
Toshinobu
T
Ootaka
Tetsuya
T
Kohzuki
Masahiro
M
D055011:Ablation Techniques; D000199:Actins / Q000378:metabolism; D000818:Animals; D000959:Antihypertensive Agents / Q000627:therapeutic use*; D001383:Azetidinecarboxylic Acid / Q000031:analogs & derivatives / Q000627:therapeutic use; D001806:Blood Urea Nitrogen; D003131:Combined Modality Therapy; D003404:Creatinine / Q000097:blood; D004095:Dihydropyridines / Q000627:therapeutic use; D005081:Exercise Therapy; D007093:Imidazoles / Q000627:therapeutic use; D007668:Kidney / Q000378:metabolism; D007676:Kidney Failure, Chronic / Q000188:drug therapy / Q000378:metabolism / Q000628:therapy*; D008297:Male; D011507:Proteinuria / Q000378:metabolism; D051381:Rats; D011921:Rats, Inbred WKY; D013777:Tetrazoles / Q000627:therapeutic use
D000199:Actins; D000959:Antihypertensive Agents; D001383:Azetidinecarboxylic Acid; D003404:Creatinine; D004095:Dihydropyridines; D007093:Imidazoles; D013777:Tetrazoles; C498862:Acta2 protein, rat; C437965:olmesartan; C061679:azelnidipine