Blocking both type A and B endothelin receptors in the kidney attenuates renal injury and prolongs survival in rats with remnant kidney

American Journal of Kidney Diseases : the Official Journal of the National Kidney Foundation
A BenigniG Remuzzi

Abstract

Renal disease progression in the rat is associated with a time-dependent upregulation of renal endothelin-1 (ET-1) gene expression and synthesis. We have previously demonstrated that endothelin A receptor subtype (ETA) blockade in rats with remnant kidney reduced signs of disease activity, suggesting that ET-1 exerts part of its deleterious effects on the kidney through ETA. No data are available so far on the role of ETB receptor in progressive renal injury. We first studied renal ETA and ETB receptor gene expression in rats with remnant kidney on days 7, 30, and 120 after the surgical procedure. While renal expression of ETA was unaffected, ETB receptor gene was significantly upregulated with time in rats with remnant kidney, being 3.5-fold and sixfold higher than shamoperated rats at days 30 and 120. We also evaluated whether bosentan, a nonpeptidic ETA and ETB receptor antagonist, offered better protection against renal disease progression than reported for ETA-selective blockers and whether it improved survival in animals with renal ablation. Two groups of rats with renal mass reduction (n = 11 each) were given bosentan 100 mg/kg/d orally or its vehicle (carboxymethyl cellulose) beginning day 7 after the surgical procedure...Continue Reading

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Sep 12, 2000·Current Hypertension Reports·L D Dworkin, D G Shemin
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