Role for endothelin in the renal responses to radiocontrast media in the rat.
1. The involvement of endothelin in the renal responses to radiocontrast media was examined in the rat in vitro and in vivo using BQ123, a selective endothelin (ETA) receptor antagonist, and phosphoramidon, an endothelin-converting enzyme inhibitor. 2. For experiments in vitro, an isolated perfused rat kidney was employed perfusing in closed circuit with an albumin-based Krebs-Henseleit solution. The effects of BQ123 and phosphoramidon on the renal responses to iotrolan (iso-osmolar radiocontrast media) and diatrizoate (high-osmolar radiocontrast media) were examined. In vivo, renal conductance was measured using a Doppler flow probe in the anaesthetized rat pretreated with indomethacin, and the effects of BQ123 and phosphoramidon on the renal response to intravenous diatrizoate were examined. 3. In vitro, iotrolan and diatrizoate both produced a biphasic effect on the glomerular filtration rate, characterized by a transient increase followed by a sustained fall. Pretreatment with BQ123 (10 mumol/l), but not phosphoramidon (1 mmol/l), prevented both the increase and the sustained fall in glomerular filtration rate induced by radiocontrast media. 4. In vitro, iotrolan and diatrizoate both produced a sustained fall in renal perfusate flow. An initial increase in renal perfusate flow was only observed with diatrizoate. Pretreatment with BQ123 (10 mumol/l), but not with phosphoramidon (1 mmol/l), markedly inhibited the sustained fall in renal perfusate flow produced by both iotrolan and diatrizoate. BQ123 (10 mumol/l), however, markedly potentiated the renal vasodilatation produced by diatrizoate.(ABSTRACT TRUNCATED AT 250 WORDS)
Sheffield Kidney Institute, Northern General Hospital, U.K.
S
S
Oldroyd
S J
SJ
Slee
J
J
Haylor
S K
SK
Morcos
C
C
Wilson
D000818:Animals; D016282:Aspartic Acid Endopeptidases / Q000037:antagonists & inhibitors; D003287:Contrast Media / Q000494:pharmacology*; D003973:Diatrizoate / Q000494:pharmacology; D065128:Endothelin Receptor Antagonists; D000072396:Endothelin-Converting Enzymes; D016232:Endothelins / Q000502:physiology*; D005919:Glomerular Filtration Rate / Q000187:drug effects; D006020:Glycopeptides / Q000494:pharmacology; D007668:Kidney / Q000187:drug effects* / Q000502:physiology; D008297:Male; D008666:Metalloendopeptidases; D009924:Organ Culture Techniques; D010456:Peptides, Cyclic / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D014283:Triiodobenzoic Acids / Q000494:pharmacology
D003287:Contrast Media; D065128:Endothelin Receptor Antagonists; D016232:Endothelins; D006020:Glycopeptides; D010456:Peptides, Cyclic; D014283:Triiodobenzoic Acids; D003973:Diatrizoate; C033300:iotrolan; D016282:Aspartic Acid Endopeptidases; D008666:Metalloendopeptidases; D000072396:Endothelin-Converting Enzymes; C072247:cyclo(Trp-Asp-Pro-Val-Leu); C008890:phosphoramidon