Endothelin Receptor Antagonists (ERA) in Hypertension and Chronic
Kidney Disease: a Rose with Many Thorns

Doumas, Michael; Athyros, Vasilios G.; Katsiki, Niki; Reklou, Andromachi; Lazaridis, Αntonios; Karagiannis, Asterios

doi:10.2174/1876526201305010012

TOHYPERJ

2013

DOI: 10.2174/1876526201305010012

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Endothelin Receptor Antagonists (ERA) in Hypertension and Chronic Kidney Disease: a Rose with Many Thorns

Michael Doumas¹,

Vasilios G. Athyros²,

Niki Katsiki³

et al.

Abstract: Abstract:The discovery of endothelin created a lot of enthusiasm and paved new therapeutic avenues for the treatment of arterial hypertension. Endothelin plays a significant role in blood pressure regulation through pronounced vasoconstriction and modulation of sodium and water reabsorption in the kidneys. Endothelin receptor antagonists have been tested in many clinical trials in patients with arterial hypertension, heart failure, pulmonary arterial hypertension, systemic sclerosis, chronic kidney disease, an… Show more

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Cited by 2 publications

References 99 publications

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Endothelin-1 and the kidney

Miguel

Speed²,

Kasztan³

et al. 2016

Current Opinion in Nephrology and Hypertension

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Purpose of review The role of endothelin-1 (ET-1) in the kidney has been under study for many years; however, the complex mechanisms by which endothelin controls the physiology/pathophysiology of this organ are not fully resolved. This review aims to summarize recent findings on the field, especially regarding glomerular and tubular damage, Na+/water homeostasis and sex differences in ET-1 function. Recent findings Podocytes have been recently identified as a target of ET-1 in the glomerular filtration barrier via ETA receptor (ETAR) activation. Activation of ETAR by ET-1 leads to renal tubular damage by promoting endoplasmic reticulum stress and apoptosis in these cells. In addition, high flow rates in the nephron in response to high salt intake induce ET-1 production by collecting ducts and promote nitric oxide dependent natriuresis through ENaC inhibition. Recent evidence also indicates that sex hormones regulate the renal ET-1 system differently in males and females, with estrogen suppressing renal ET-1 production and testosterone upregulating that production. Summary Based on the reports reviewed in here, targeting of the renal ET system is a possible therapeutic approach against the development of glomerular injury. More animal and clinical studies are needed to better understand the dimorphic control of this system by sex hormones.

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Endothelin-1 and the kidney

Miguel

Speed²,

Kasztan³

et al. 2016

Current Opinion in Nephrology and Hypertension

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The Role of Endothelin and Endothelin Antagonists in Chronic Kidney Disease

et al. 2019

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Background: Endothelins (ET) are a family of peptides that act as potent vasoconstrictors and pro-fibrotic growth factors. ET-1 is integral to renal and cardiovascular pathophysiology and exerts effects via autocrine, paracrine and endocrine signaling pathways tied to regulation of aldosterone, catecholamines, and angiotensin. In the kidney, ET-1 is critical to maintaining renal perfusion and controls glomerular arteriole tone and hemodynamics. It is hypothesized that ET-1 influences the progression of chronic kidney disease (CKD), and the objective of this review is to discuss the pathophysiology, and role of ET and endothelin receptor antagonists (ERAs) in CKD. Summary: The use of ERAs in hypertensive nephropathy has the potential to decrease proteinuria, and in diabetic nephropathy has the potential to restore glycocalyx thickness, also decreasing proteinuria. Focal segmental glomerular sclerosis has no specific Food and Drug Administration-approved therapy currently, however, ERAs show promise in decreasing proteinuria and slowing tissue damage. ET-1 is a potential biomarker for autosomal dominant polycystic kidney disease progression and so it is thought that ERAs may be of some therapeutic benefit. Key Messages: Multiple studies have shown the utility of ERAs in CKD. These agents have shown to reduce blood pressure, proteinuria, and arterial stiffness. However, more clinical trials are needed, and the results of active or recently concluded studies are eagerly awaited.

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Endothelin Receptor Antagonists (ERA) in Hypertension and Chronic Kidney Disease: a Rose with Many Thorns

Cited by 2 publications

References 99 publications

Endothelin-1 and the kidney

Endothelin-1 and the kidney

The Role of Endothelin and Endothelin Antagonists in Chronic Kidney Disease

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