ROLE FOR ENDOTHELIN IN THE RENAL RESPONSES TO RADIOCONTRAST MEDIA IN THE RAT

1. The involvement of endothelin in the renal responses to radiocontra st media was examined in the rat in vitro and in vivo using BQ123, a s elective endothelin (ET(A)) receptor antagonist, and phosphoramidon, a n endothelin-converting enzyme inhibitor. 2. For experiments in vitro, an isolated perfused rat kidney was employed perfusing in closed circ uit with an albumin-based Krebs-Henseleit solution. The effects of BQ1 23 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 Doppl er flow probe in the anaesthetized rat pretreated with indomethacin, a nd the effects of BQ123 and phosphoramidon on the renal response to in travenous diatrizoate were examined. 3. In vitro, iotrolan and diatriz oate both produced a biphasic effect on the glomerular filtration rate , characterized by a transient increase followed by a sustained fall. Pretreatment with BQ123 (10 mu mol/l), but not phosphoramidon (1 mmol/ l), prevented both the increase and the sustained fall in glomerular f iltration rate induced by radiocontrast media. 4. In vitro, iotrolan a nd diatrizoate both produced a sustained fall in renal perfusate flow. An initial increase in renal perfusate flow was only observed with di atrizoate. Pretreatment with BQ123 (10 mu mol/l), but not with phospho ramidon (1 mmol/l), markedly inhibited the sustained fall in renal per fusate flow produced by both iotrolan and diatrizoate. BQ123 (10 mu mo l/l), however, markedly potentiated the renal vasodilatation produced by diatrizoate. 5. In vivo, in the anaesthetized rat treated with indo methacin, the sustained fall in renal conductance produced by diatrizo ate (2.9 g of iodine/kg, intravenously) was markedly inhibited by pret reatment with BQ123 (1 mg/kg) but not with phosphoramidon (10 mg/kg). 6. A role for endothelin as a mediator of the renal responses of radio contrast media is proposed.