Role of endothelin and endothelin receptor antagonists in renal disease

  title={Role of endothelin and endothelin receptor antagonists in renal disease},
  author={Wolfgang Neuhofer and David Pittrow},
  journal={European Journal of Clinical Investigation},
  • 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… 
Endothelin receptor selectivity in chronic kidney disease: rationale and review of recent evidence
Although preliminary data in humans are promising, the potential role of ERAs in patients with CKD and the question of which receptor subtype should be targeted can only be clarified in randomized clinical trials.
Regulation of blood pressure and salt homeostasis by endothelin.
This review provides a detailed analysis of how the ET system is involved in the control of blood pressure and Na homeostasis, focusing primarily on physiological regulation with some discussion of the role of theET system in hypertension.
Endothelin signaling and actions in the renal mesangium.
  • A. Sorokin
  • Biology, Medicine
    Contributions to nephrology
  • 2011
Plentiful evidence suggests an essential role of ET-1-signaling and action in the renal mesangium for renal biology and pathobiology in diabetes, hypertension, and glomerulonephritis.
Endothelin and tubulointerstitial renal disease.
Role of endothelin receptor A and NADPH oxidase in vascular abnormalities
  • D. Dai, Y. Dai
  • Medicine, Biology
    Vascular health and risk management
  • 2010
Endothelin receptor antagonist CPU0213 and ingredients from plant origins such as CPU86017, p-benzyl-tetra-hydro-berberine are effective in attenuating vascular abnormality by normalizing changes of biomarkers in the vascular wall.
Endothelin-1 Induces Proteinuria by Heparanase-Mediated Disruption of the Glomerular Glycocalyx.
The data suggest that in diabetes, endothelin-1 signaling, as occurs in endothelial activation, induces heparanase expression in the podocyte, damage to the glycocalyx, proteinuria, and renal failure, and prevention of these effects may constitute the mechanism of action ofendothelin receptor blockers in DN.
Inhibition of ENaC by endothelin-1.
Argirein alleviates diabetic nephropathy through attenuating NADPH oxidase, Cx43, and PERK in renal tissue
Argirein with two active molecules rhein and l-arginine may be effective in suppressing the inflammatory cytokines contributing to the pathogenesis of DN and is potential in alleviating and retarding microvascular complications of diabetes such as DN in clinical settings.
Lack of renal improvement with nonselective endothelin antagonism with tezosentan in type 2 hepatorenal syndrome
An endothelin receptor blockade potentially can cause a deterioration in renal function in patients with cirrhosis and type 2 HRS, and caution should be taken in future studies using endothelins receptor antagonists in these patients.


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.
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
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.
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
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
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.
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.
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.
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.
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.