[The role of endothelin in the progression of the renal disease in an experimental model of chronic kidney failure].
Recent in vitro and in vivo data suggest that endothelin, a potent vasoconstrictor peptide originally isolated from cultured porcine aortic endothelial cells, may be one of the factors accounting for progressive glomerulosclerosis in experimental and human glomerulopathies. Endothelin is expressed and produced by glomerular endothelial and mesangial cells in culture, has a mitogenic effect on mesangial cells and stimulates mesangial synthesis of extracellular matrix components such as type I, III and IV collagen and laminin. In rats with renal mass ablation, a model of chronic renal disease characterized by systemic hypertension, proteinuria and progressive glomerulosclerosis, a significant increase in urinary excretion of endothelin was documented 45 days after surgery as compared with basal values. Experiments involving the infusion of labeled endothelin into renal arteries of rats with renal mass ablation have suggested that the enhanced urinary excretion rate of endothelin could reflect an increased renal production of the peptide. Recent experiments done with Northern blot analysis have evidenced a 2.5 fold increase in pre-proendothelin transcript in kidney homogenates from rats with remnant kidney at 30 days after surgery. The increase averaged 4-5 fold at 60 and 120 days. In the same animals a significant correlation was found between urinary endothelin excretion and the percent of glomeruli affected by glomerulosclerosis. We conclude that the progression of renal disease after surgical ablation of renal mass is associated with an increased renal endothelin gene expression together with excessive urinary excretion of the corresponding protein. It is speculated that endothelin may mediate glomerular structural abnormalities associated with the progression of renal disease.
Orisio
S
S
Zoja
C
C
Remuzzi
G
G
D000818:Animals; D004195:Disease Models, Animal; D016232:Endothelins / Q000494:pharmacology / Q000502:physiology*; D005923:Glomerulosclerosis, Focal Segmental / Q000209:etiology / Q000503:physiopathology; D007668:Kidney / Q000187:drug effects / Q000503:physiopathology; D007676:Kidney Failure, Chronic / Q000209:etiology* / Q000503:physiopathology; D051381:Rats; D017466:Receptors, Endothelin / Q000502:physiology
D016232:Endothelins; D017466:Receptors, Endothelin
Ruolo dell'endotelina nella progressione della malattia renale in un modello sperimentale di insufficienza renale cronica.