Role for Endothelin in the Renal Responses to Radiocontrast Media in the Rat

Abstract

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 μmol/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 μmol/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 μmol/l), however, markedly potentiated the renal vasodilatation produced by diatrizoate. 5. In vivo, in the anaesthetized rat treated with indomethacin, the sustained fall in renal conductance produced by diatrizoate (2.9 g of iodine/kg, intravenously) was markedly inhibited by pretreatment 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 radiocontrast media is proposed.