Endothelin receptors, renal effects and blood pressure

Boesen, Erika I.

doi:10.1016/j.coph.2014.12.007

Cited by 42 publications

(24 citation statements)

References 92 publications

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“…The renal injury induced by ischemia was ameliorated by atrasentan (∼1200-fold greater affinity for ET A compared to ET B ) in a mouse model of unilateral renal ischemia [35]. Further preclinical evidence suggests the potential for benefit of ERAs in preventing microvascular rarefaction and fibrosis in renal artery stenosis [36]. In a rat model of malignant hypertension, combined ERA and angiotensin receptor antagonism with avosentan and valsartan reduced albuminuria greater than either agent alone [37•].…”

Section: Endothelin Receptor Antagonists and Renoprotectionmentioning

confidence: 99%

Endothelin Receptor Antagonists: New Hope for Renal Protection?

2015

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Endothelin receptor antagonists (ERAs) have the potential to be a new paradigm in the treatment of chronic kidney disease (CKD). ERAs inhibit the effects of endothelin-1 (ET-1), which is known to promote CKD by causing renal cellular injury, proteinuria, inflammation, fibrosis, and hypertrophy. ERAs have been extensively studied preclinically in models of CKD and now in a large clinical trial to determine their effect on slowing the progression of CKD. Initial clinical trials show promise with regard to ERA effects on reducing proteinuria in patients with diabetic nephropathy (DN) who are already on renin-angiotensin system (RAS) blocking agents. A common side effect of peripheral edema has been consistently reported in clinical trials using ERAs; hence, finding a safe balance between renoprotective actions and side effects needs to be achieved.

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Section: Endothelin Receptor Antagonists and Renoprotectionmentioning

confidence: 99%

Endothelin Receptor Antagonists: New Hope for Renal Protection?

2015

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“…ET-1 stimulates two G proteincoupled receptor subtypes, ET A and ET B receptors, with the same affinity for both receptors (7). Activation of each receptor subtype leads to different, and often opposite, physiological and pathophysiological results (3). Renal cortical and inner medullary tubules are rich in ET B receptors, whereas outer medullary tubules express both ET A and ET B receptors.…”

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confidence: 99%

Endothelium-derived ET-1 and the development of renal injury

Miguel

Pollock

2015

American Journal of Physiology-Regulatory, Integrative and Comp

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De Miguel C, Pollock DM, Pollock JS. Endothelium-derived ET-1 and the development of renal injury. Am J Physiol Regul Integr Comp Physiol 309: R1071-R1073, 2015. First published May 20, 2015 doi:10.1152/ajpregu.00142.2015.-The role of the vasoactive peptide endothelin-1 (ET-1) in renal injury is not fully understood. In this review, we examine the genetic models available to understand the autocrine/paracrine mechanisms by which ET-1 leads to renal injury and propose the working hypothesis that endothelium-derived ET-1 induces renal injury by initiating renal tubular apoptosis in a paracrine manner.endothelin-1; apoptosis; renal injury ENDOTHELIN-1 (ET-1) is an endogenous 21 amino acid peptide that has powerful vasoactive properties. ET-1 is produced by many cell types including endothelial cells (40), cardiomyocytes (36), mesangial cells (31), and different segments of the nephron, especially collecting ducts (22). Increased activity of the ET-1 system has been described in several cardiovascular and renal diseases (25,28). ET-1 stimulates two G proteincoupled receptor subtypes, ET A and ET B receptors, with the same affinity for both receptors (7). Activation of each receptor subtype leads to different, and often opposite, physiological and pathophysiological results (3). Renal cortical and inner medullary tubules are rich in ET B receptors, whereas outer medullary tubules express both ET A and ET B receptors. Overactivation of the renal ET A pathway leads to hypertrophy, inflammation, and fibrosis. Actions of the ET B pathway promote clearance of ET-1 from circulation, stimulation of nitric oxide, and/or prostacyclin release, as well as increased sodium and water excretion (23). Several cell-type-specific endothelin pathway knockout mouse models and an ET B receptor-deficient rat model facilitate in-depth investigations into the activation of cellular source(s) and actions of ET-1. This review highlights the rationale for the use of genetic rodent models to elucidate the autocrine and/or paracrine mechanisms of ET-1-dependent development of renal apoptosis and injury. Based on the literature and our own preliminary findings, studying tunicamycin-induced renal apoptosis in two ET-1 genetic rodent models provides rationale for a working hypothesis that endothelium-derived ET-1 induces renal tubular apoptosis by a paracrine mechanism. ET-1 Pathway, Apoptosis, and Renal InjuryRenal injury is preceded by tubular apoptosis and loss of nephrons (26). Apoptotic cell death is characterized by a series of changes in cellular morphology, such as shrinkage of the cell membrane, condensation of nuclear chromatin, cellular fragmentation, and engulfment of the apoptotic bodies by neighboring cells (21). Different vasoactive peptides have been implicated in the regulation of cellular apoptosis; however, contradictory reports in the literature do not provide a clear role of ET-1 in apoptosis and renal injury. Some studies indicate that ET-1 attenuates apoptosis in vascular smooth muscle cells (39), endothelial cells (11), and...

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“…Renal injury is initially characterized by renal tubular cell apoptosis and nephron loss. Additionally, the ET‐1 system was reported to induce apoptosis of renal tubules through paracrine, and it can mediate renal parenchymal injury, followed by inflammation and other effects . Therefore, serum ET‐1 was measured to investigate its sensitivity to AKI by high‐pressure renal pelvic perfusion.…”

Section: Introductionmentioning

confidence: 99%

Acute renal impairment characterization using diffusion magnetic resonance imaging: Validation by histology

Zhu

et al. 2019

NMR in Biomedicine

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Diffusion magnetic resonance imaging has been demonstrated to be a simple, noninvasive and accurate method for the detection of renal microstructure and microcirculation, which are closely linked to renal function. Moreover, serum endothelin‐1 (ET‐1) was also reported as a good indicator of early renal injury. The aim of this study was to evaluate the feasibility and capability of diffusion MRI and ET‐1 to detect acute kidney injury by an operation simulating high‐pressure renal pelvic perfusion, which is commonly used during ureteroscopic lithotripsy. Histological findings were used as a reference. Fourteen New Zealand rabbits in an experimental group and 14 in a control group were used in this study. Diffusion tensor imaging and intravoxel incoherent motion diffusion‐weighted imaging were acquired by a 3.0 T MRI scanner. Significant corticomedullary differences were found in the values of the apparent diffusion coefficient (ADC), pure tissue diffusion, volume fraction of pseudo‐diffusion (fp) and fractional anisotropy (FA) (P < 0.05 for all) in both preoperation and postoperation experimental groups. Compared with the control group, the values of cortical fpmean, medullary ADCmean and FAmean decreased significantly (P < 0.05) after the operation in the experimental group. Also, the change rate of medullary ADCmean in the experimental group was more pronounced than that in the control group (P = 0.018). No significant change was found in serum ET‐1 concentration after surgery in either the experimental (P = 0.80) or control (P = 0.17) groups. In the experimental group, histological changes were observed in the medulla, while no visible change was found in the cortex. This study demonstrated the feasibility of diffusion MRI to detect the changes of renal microstructure and microcirculation in acute kidney injury, with the potential to evaluate renal function. Moreover, the sensitivity of diffusion MRI to acute kidney injury appears to be superior to that of serum ET‐1.

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Endothelin receptors, renal effects and blood pressure

Cited by 42 publications

References 92 publications

Endothelin Receptor Antagonists: New Hope for Renal Protection?

Endothelin Receptor Antagonists: New Hope for Renal Protection?

Endothelium-derived ET-1 and the development of renal injury

Acute renal impairment characterization using diffusion magnetic resonance imaging: Validation by histology

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