Open AccessUpregulation of Renal Endothelin Receptors in Glycerol-Induced Acute Renal Failure in the Rat
Author(s) -
Pierre Roubert,
S. Cornet,
Pascal Plas,
C. Guilmard,
E. Pirotzky,
P Chabrier,
P. Braquet
Publication year - 1993
Publication title -
journal of cardiovascular pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.762
H-Index - 100
eISSN - 1533-4023
pISSN - 0160-2446
DOI - 10.1097/00005344-199322008-00079
Subject(s) - endocrinology , renal cortex , medicine , glycerol , renal medulla , kidney , endothelin receptor , tonicity , receptor , renal function , downregulation and upregulation , chemistry , biology , biochemistry , gene
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.