Effect of the selective adenosine A1-receptor antagonist KW-3902 on tubuloglomerular feedback in radiocontrast-media-induced nephropathy in rats with chronic nitric oxide deficiency.
To study the possible mechanism of renoprotective effects of adenosine A1-receptor antagonist against radiocontrast media (RCM)-induced nephropathy, we investigated the effects of adenosine A1-receptor antagonist on tubuloglomerular feedback (TGF) activity prior to and following application of RCM in chronic NO-depleted rats. TGF in NO-depleted rats was significantly enhanced compared with that in normal rats. After RCM application, the enhanced TGF was continued. A selective adenosine A1-receptor antagonist, KW-3902 (8-(noradamantan-3-yl)-1,3-dipropylxanthine), inhibited the enhanced TGF. These results suggest that KW-3902 could inhibit TGF in chronic NO-depleted rats. Renoprotective effects by adenosine antagonists could be partly due to an inhibition of TGF via the blockade of the adenosine A1-receptor.
Yao
K
K
Drug Development Research Laboratories, Pharmaceutical Research Institute, Kyowa Hakko Kogyo Co., Ltd., Shizuoka, Japan. kozo.yao@kyowa.co.jp
Heyne
N
N
Osswald
H
H
D000818:Animals; D002908:Chronic Disease; D003287:Contrast Media / Q000009:adverse effects*; D007674:Kidney Diseases / Q000139:chemically induced / Q000188:drug therapy* / Q000503:physiopathology; D007678:Kidney Glomerulus / Q000503:physiopathology*; D007684:Kidney Tubules / Q000503:physiopathology*; D008297:Male; D009569:Nitric Oxide / Q000172:deficiency*; D058915:Purinergic P1 Receptor Antagonists; D051381:Rats; D017207:Rats, Sprague-Dawley; D014970:Xanthines / Q000494:pharmacology / Q000627:therapeutic use*
D003287:Contrast Media; D058915:Purinergic P1 Receptor Antagonists; D014970:Xanthines; D009569:Nitric Oxide; C073525:rolofylline