Upregulation of renal endothelin receptors in glycerol-induced acute renal failure in the rat.
Acute renal failure was induced in rat with a hypertonic glycerol solution and endothelin-1 (ET-1) binding was measured in kidney membrane preparations. In control animals, [125I]-ET-1 bound to specific recognition sites in kidney cortex (Bmax = 134 +/- 11 fmol/mg protein) and medulla (Bmax = 300 +/- 9 fmol/mg protein) with an apparent dissociation constant (Kd) of 0.16 +/- 0.06 nM and 0.39 +/- 0.07 nM for cortex 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 48 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) and 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 significantly 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 Kd values. These results suggest that upregulation of ET-1 receptors is involved in renal hemodynamic impairment induced by glycerol.
Roubert
P
P
Institut Henri Beaufour, Les Ulis, France.
Cornet
S
S
Plas
P
P
Guilmard
C
C
Pirotzky
E
E
Chabrier
P E
PE
Braquet
P
P
D058186:Acute Kidney Injury / Q000139:chemically induced / Q000378:metabolism*; D000818:Animals; D003404:Creatinine / Q000097:blood; D016232:Endothelins / Q000378:metabolism; D005990:Glycerol; D007457:Iodine Radioisotopes; D007668:Kidney / Q000187:drug effects / Q000378:metabolism*; D007672:Kidney Cortex / Q000187:drug effects / Q000378:metabolism; D007679:Kidney Medulla / Q000187:drug effects / Q000378:metabolism; D008297:Male; D008566:Membranes / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D017466:Receptors, Endothelin / Q000187:drug effects*; D015854:Up-Regulation / Q000187:drug effects*; D014508:Urea / Q000097:blood
D016232:Endothelins; D007457:Iodine Radioisotopes; D017466:Receptors, Endothelin; D014508:Urea; D003404:Creatinine; D005990:Glycerol