Effects of adenosine receptor antagonists on the responses to contrast media in the isolated rat kidney.
Contrast media can induce both a decrease in renal blood flow and a reduction in glomerular filtration rate (GFR) when administered to both experimental animals and humans. In the present study we have examined the role of adenosine in mediating these effects using the isolated perfused rat kidney. Kidneys were perfused with a 6. 7%-(w/v)-albumin-based perfusate supplemented with glucose and amino acids (n=6 per group). They were exposed to diatrizoate [20 mg of iodine (mgI)/ml; osmolality 1650 mOsm/kg of water] or iotrolan (20 mgI/ml; osmolality 320 mOsm/kg of water) in the presence or absence of theophylline (10.8 microg/ml), or to diatrizoate in the presence or absence of a specific adenosine A(1) receptor antagonist (KW-3902; 2 microg/ml) or a specific A(2) receptor antagonist (KF17837; 6 microg/ml). Diatrizoate (n=6) produced a fall in GFR from 0.65+/-0.04 to 0.42+/-0.03 ml.min(-1).g(-1) (P<0.05); renal perfusate flow (RPF) also declined, from 36.5+/-3.8 to 22.0+/-3.2 ml. min(-1).g(-1) (P<0.05). Iotrolan (n=6) produced a fall in GFR from 0. 64+/-0.02 to 0.48+/-0.04 ml.min(-1).g(-1) (P<0.05) and in RPF from 33.3+/-3.8 to 24.0+/-3.0 ml.min(-1).g(-1) (P<0.05). Theophylline (10.8 microg/ml) prevented the fall in GFR caused by either diatrizoate (baseline, 0.63+/-0.05 ml.min(-1).g(-1); diatrizoate+theophylline, 0. 60+/-0.04 ml.min(-1).g(-1)) or iotrolan (baseline, 0.64+/-0.04 ml. min(-1).g(-1); iotrolan+theophylline, 0.67+/-0.05 ml.min(-1).g(-1)), but did not affect the decreases in RPF caused by either agent. KW-3902 (2 microg/ml) also prevented the fall in GFR produced by diatrizoate (baseline, 0.66+/-0.05 ml.min(-1).g(-1); diatrizoate+KW-3902, 0.61+/-0.05 ml.min(-1).g(-1)), while the fall in RPF remained unaffected. KF17837 (6 microg/ml) had no effect on the decreases in either GFR or RPF induced by diatrizoate (n=6 per group). The results suggest a role for adenosine acting at the A(1) receptor in mediating the decrease in GFR induced by contrast media. This effect is independent of a change in renal vascular resistance, and possibly secondary to mesangial cell contraction causing a decrease in the ultrafiltration coefficient.
Oldroyd
S D
SD
Sheffield Kidney Institute (University Division of Clinical Sciences NGH), Northern General Hospital, Herries Road, Sheffield S5 7AU, UK.
Fang
L
L
Haylor
J L
JL
Yates
M S
MS
El Nahas
A M
AM
Morcos
S K
SK
D000241:Adenosine / Q000502:physiology*; D000704:Analysis of Variance; D000818:Animals; D003287:Contrast Media / Q000494:pharmacology*; D003973:Diatrizoate / Q000494:pharmacology; D005919:Glomerular Filtration Rate / Q000187:drug effects; D007668:Kidney / Q000187:drug effects* / Q000503:physiopathology; D008297:Male; D010477:Perfusion; D010726:Phosphodiesterase Inhibitors / Q000494:pharmacology; D058915:Purinergic P1 Receptor Antagonists; D051381:Rats; D017208:Rats, Wistar; D013806:Theophylline / Q000494:pharmacology; D014283:Triiodobenzoic Acids / Q000494:pharmacology; D014970:Xanthines / Q000494:pharmacology
D003287:Contrast Media; D010726:Phosphodiesterase Inhibitors; D058915:Purinergic P1 Receptor Antagonists; D014283:Triiodobenzoic Acids; D014970:Xanthines; D003973:Diatrizoate; C081198:KF 17837; C033300:iotrolan; C073525:rolofylline; D013806:Theophylline; D000241:Adenosine