Jpn. J. Pharmacol. 84 (3), 347-350 (2000)

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

Kozo Yao1,*, Nils Heyne2 and Hartmut Osswald2

1Drug Development Research Laboratories, Pharmaceutical Research Institute, Kyowa Hakko Kogyo Co., Ltd., 1188 Shimotogari, Nagaizumi-cho, Sunto-gun, Shizuoka 411-8731, Japan
2Department of Pharmacology, Faculty of Medicine, University of Tčbingen, Wilhelmstr. 56, 72074 Tčbingen, FRG
*Corresponding author.╩╩FAX:+81-559-86-7430

Abstract: 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.

Keywords: Contrast media, Adenosine, Tubuloglomerular feedback

Copyrightę The Japanese Pharmacological Society 2000

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