We found a match
Your institution may have access to this item. Find your institution then sign in to continue.
- Title
An orally active ET<sub>A</sub>/ET<sub>B</sub> receptor antagonist ameliorates proteinuria and glomerular lesions in rats with proliferative nephritis.
- Authors
Gómez-Garre, Dulcenombre; Largo, Raquel; Xue-Hui Liu; Gutierrez, Sylvia; López-Armada, M. Jos&ecute;; Palacios, Itziar; Egido, Jesús
- Abstract
The proliferation of mesangial cells and the extracellular matrix expansion constitute the most outstanding morphological aspects of the majority of progressive glomerular diseases. In vitro, endothelin-1 (ET-1) is mitogenic for mesangial cells and induces matrix protein synthesis. We studied the possible participation of ET-1 in the pathogenesis of renal damage in a normotensive model of proliferative nephritis. Coincidentally with maximal proteinuria and glomerular lesions, an increase was found in the glomerular mRNA expression of preproET-1 and the ETA receptor (10 and 6 times compared to controls, respectively), but not of the ETB receptor, and in ET-1 urinary excretion (217 ± 33 vs.84 ± 4 pg ET-1/24 hr, N = 4 to 5, P < 0.005). By in situ hybridization, an increase in preproET-1 mRNA expression in glomerular endothelial, epithelial and mesangial cells, and in some tubular cells was observed. The administration of bosentan, an ETA/ETB receptor antagonist, had in beneficial effect on the evolution of nephritis, preventing the appearance of intense proteinuria (76 ± 35 vs. 380 ± 77 mg/24 hr, N = 4 to 5, P < 0.05), the morphological lesions and the renal function impairment (creatinine clearance 367 ± 46 vs. 268 ± 33 μl/min/100 g, N = 4 to 5). Simultaneously, there was a decrease in ET-1 urinary excretion (88 ± 14 vs. 217 ± 33 pgET-1/24 hr, N = 4.5. P < 0.05) and in the renal preproET-1 mRNA expression. The mean systolic blood pressures remained in the normal range in all animals. These data indicate that ET-1 participates in the pathogenesis of proteinuria and glomerular injury in a model of proliferative nephritis. The nonpeptidic orally active ETA/ETB receptor antagonists could be useful in the treatment of some human nephritis.
- Subjects
PROTEINURIA; EXTRACELLULAR matrix proteins; KIDNEY diseases; KIDNEY glomerulus diseases; URINALYSIS; NEPHROLOGY
- Publication
Kidney International, 1996, Vol 50, Issue 3, p962
- ISSN
0085-2538
- Publication type
Article
- DOI
10.1038/ki.1996.397