Role of endothelin and endothelin receptor antagonists in renal disease

@article{Neuhofer2006RoleOE,
  title={Role of endothelin and endothelin receptor antagonists in renal disease},
  author={Wolfgang Neuhofer and David Pittrow},
  journal={European Journal of Clinical Investigation},
  year={2006},
  volume={36}
}
  • W. Neuhofer, D. Pittrow
  • Published 1 September 2006
  • Biology, Medicine
  • European Journal of Clinical Investigation
Endothelin (ET)‐1 is a potent vasoconstrictor peptide with pro‐inflammatory, mitogenic, and pro‐fibrotic properties that is closely involved in both normal renal physiology and pathology. ET‐1 exerts a wide variety of biological effects, including constriction of cortical and medullary vessels, mesangial cell contraction, stimulation of extracellular matrix production, and inhibition of sodium and water reabsorption along the collecting duct, effects that are primarily mediated in an autocrine… 
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TLDR
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TLDR
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References

SHOWING 1-10 OF 128 REFERENCES
Endothelins in the normal and diseased kidney.
  • D. Kohan
  • Medicine, Biology
    American journal of kidney diseases : the official journal of the National Kidney Foundation
  • 1997
Physiology and pathology of endothelin-1 in renal mesangium.
TLDR
The present understanding of how ET-1 is involved in mesangial function in health and disease is examined and the status of clinical trials using ET antagonists, which have only been conducted in nonrenal disease, are discussed as a background for advocating their use in diseases characterized by excessive MC-derivedET-1.
Effects of Endothelin Receptor Antagonists on the Progression of Diabetic Nephropathy
TLDR
It is indicated that ETA receptor antagonists as well as combined ETA/ETB receptor antagonists reduce proteinuria and completely normalize the renal matrix protein expression in hyperglycemic rats with streptozotocin-induced diabetes.
Unselective inhibition of endothelin receptors reduces renal dysfunction in experimental diabetes.
TLDR
Data suggest that ET-1 is a contributory mediator of kidney damage in diabetes and indicate that ET receptor antagonists may represent a new therapeutic mean for treatment of progressive diabetic nephropathy.
Role of endothelin in fibrosis and anti‐fibrotic potential of bosentan
TLDR
The anti‐fibrotic effects of bosentan extend to fibrosis induced by mediators other than endothelin such as transforming growth factor‐beta, angiotensin II and aldosterone, indicating a central role ofendothelin and endothelins receptors in fibrotic processes.
Angiotensin II Blockade Limits Tubular Protein Overreabsorption and the Consequent Upregulation of Endothelin 1 Gene in Experimental Membranous Nephropathy
TLDR
A link between excessive protein tubular reabsorption and enhanced renal ET-1 in chronic nephropathies is suggested and provided a novel explanation for the renoprotective effect in vivo of drugs that, by blocking the biological activity of angiotensin II, reduce glomerular protein traffic and possible deleterious effects of excessive tubular protein overloading.
Renal endothelin-1 and endothelin receptor type B expression in glomerular diseases with proteinuria.
TLDR
It is concluded that the increased ET-R(B) and ET-1 mRNA and protein expression observed in animal models of renal disease is also demonstrable among patients with renal disease and high-grade proteinuria.
Combined antagonism of endothelin A/B receptors links endothelin to vasoconstriction whereas angiotensin II effects fibrosis. Studies in chronic cyclosporine nephrotoxicity in rats.
TLDR
Despite striking functional preservation in response to antagonism of Et receptors, tubular vacuolization/dilatation, as well as arteriolopathy, was not different among the CsA-treated groups.
A specific endothelin subtype A receptor antagonist protects against injury in renal disease progression.
TLDR
The results showed that ETA receptor blocker reduced the abnormal permeability to proteins, limited glomerular injury and prevented renal function deterioration thus confirming the working hypothesis and suggesting that this class of compounds may eventually prove useful in the treatment of human progressive nephropathies.
Endothelin system: the double-edged sword in health and disease.
TLDR
The endothelin system consists of two G-protein-coupled receptors, three peptide ligands, and two activating peptidases, which have a variety of physiological and pathophysiological roles in the vessels and brain.
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