UP-REGULATION OF RENAL ENDOTHELIN RECEPTORS IN GLYCEROL-INDUCED ACUTE-RENAL-FAILURE IN THE RAT

Acute renal failure was induced in rat with a hypertonic glycerol solu tion and endothelin-1 (ET-1) binding was measured in kidney membrane p reparations. In control animals, [I-125]-ET-1 bound to specific recogn ition sites in kidney cortex (B(max) 134 +/- 11 fmol/mg protein) and m edulla (B(max) = 300 +/- 9 fmol/mg protein) with an apparent dissociat ion constant (K(d)) of 0.16 +/- 0.06 nM and 0.39 +/- 0.07 nM for corte x and medulla, respectively. A single i.m. dose of 10 ml/kg glycerol ( 50% w/v) resulted in alterations of renal function that were maximal 4 8 h after glycerol administration. After this 48-h period, serum urea was increased from 0.20 +/- 0.01 g/L to 1.16 +/- 0.20 g/L (p<0.001) an d creatinine clearance was reduced from 1.04 +/- 0.15 ml/min to 0.23 /- 0.06 ml/min (p<0.001). Renal ET-1 receptor density was significantl y increased in glycerol-treated rats to 255 +/- 14 fmol/mg protein in renal cortex (p<0.01), and 576 +/- 55 fmol/mg protein in renal medulla (p<0.01), with no significant modification of the K(d) values. These results suggest that upregulation of ET-1 receptors is involved in ren al hemodynamic impairment induced by glycerol.