Mechanisms of Chemically Induced Glomerular Injury
Robin S. Goldstein in Mechanisms of Injury in Renal Disease and Toxicity, 2020
Because of its vasoconstrictive properties, endothelin (ET) may play a major role in the control of renal hemodynamics in normal and disease conditions. CSA increases ET synthesis and release either by damaging the endothelium or by directly increasing ET gene expression, possibly in the mesangial cells.6 Cultured human mesangial cells express the gene for ET and secrete the corresponding protein.6 Active production of ET by mesangial cells might contribute to modulate glomerular vascular tone and may thus control glomerular function. Recent studies provide evidence129 that CSA induces a time-and dose-dependent decrease in size of the isolated human glomeruli and a distinct contraction of the cultured mesangial cells (Figure 14). These effects occurred in the absence of renal nervous and extraglomerular humoral influences.129 Therefore, it appears that CSA could trigger mesangial cells to increase synthesis of ET which, in turn, could act in an autocrine mode to stimulate contraction of the mesangial cells themselves, contributing in this way to the alteration of the glomerular function.
The Relation of Endothelial Cell Regulation of Contractility of the Heart to the Supply of Oxygen
Malcolm J. Lewis, Ajay M. Shah in Endothelial Modulation of Cardiac Function, 2020
There is another factor that will influence the local concentration and the effect of endothelin, namely the high concentration of endothelin receptors on endothelial cells and their high affinity for endothelin (Frelin and Guedin, 1994). The consequence of their presence should be a strong autocrine effect and buffering of the concentration at a low level in the vicinity of the vascular smooth muscle cells. Since endothelin stimulates the release of NO by endothelial cells, the result of endothelin secretion could be primarily to dilate blood vessels except under special conditions. If this is the case, the apparent mismatch between the effects of endothelin on vascular smooth muscle and cardiac myocytes might not exist. At lower concentrations of endothelin, the primary effect is vasodilation and an increase in actomyosin ATPase activity and the velocity of shortening of cardiac muscle. At higher concentrations, there is some vasoconstriction and an increase in the efficiency of myocardial contraction.
Tumor immunology
Gabriel Virella in Medical Immunology, 2019
Infiltration of tumors by immune cells is mediated by adhesion molecules on endothelial cells in the tumor vasculature. Tumor growth dysregulates adhesion molecule function by production of VEGF. In a normal state, tumor necrosis factor (TNF) promotes the expression of adhesion molecules on endothelial cells. However, in the presence of VEGF, the effect of TNF is abrogated. Many types of tumor also produce high levels of endothelin (ET). ET has also been found to affect endothelial cells leading to dysregulation of adhesion molecules. Additionally, tumor vasculature can affect the infiltration of tumor-reactive cells by expressing molecules that can directly kill T cells (e.g., Fas ligand) or by expressing immune-inhibitory molecules such as PD-L1, IL-10, and TGFβ.
Adjuncts to pulsed dye laser for treatment of port wine stains: a literature review
Published in Journal of Cosmetic and Laser Therapy, 2021
Bing Wang, Xianglin Mei, Yanlong Wang, Xin Hu, Fuqiu Li
Endothelin is a bioactive peptide synthesized by endothelial cells that has vasoconstrictive effect, which is associated with the growth of various tumors. It can inhibit cell apoptosis and promote neovascularization. Endothelin receptor antagonists have been shown to exhibit antiangiogenic effects in animal models (47). Accordingly, some scholars speculated that the endothelin receptor antagonist, bosentan, may inhibit PDL-induced angiogenesis in PWS lesions. Under this assumption, it was used in combination with PDL to treat PWS. Four patients with refractory PWS received bosentan 1 day before the PDL treatment and continued it for 14 days. Three patients showed no or only slight improvement, whereas one patient showed a noticeable improvement at the treated area. At 6-month follow-up, the efficacy was maintained. Subsequently, this patient was continued to be treated, and the lesions also showed blanching. This result indicates that some PWS patients may benefit from systematically administered endothelin receptor antagonists to inhibit angiogenesis after PDL treatment (48).
Endothelial dysfunction: a therapeutic target in bacterial sepsis?
Published in Expert Opinion on Therapeutic Targets, 2021
Jean-Louis Vincent, Can Ince, Peter Pickkers
There are three structurally similar, 21 amino acid isoforms of endothelin (ET-1, −2 and −3), which bind to two endothelin receptors (ETA and ETB). ET-1 is mainly produced by vascular endothelial cells and is a potent vasoconstrictor. An endothelin precursor (big ET-1, or pro-ET-1) consisting of 39 amino acids is cleaved by the endothelin-converting enzyme (ECE), which resides on the endothelial cell membrane, to form ET-1. ET-1 can bind to the ETA receptor on the smooth muscle cells of the vessel wall, leading to vasoconstriction via a cascade of intracellular processes (Figure 4). ET-1 can also bind to the ETB receptor located on the endothelial cell itself. Occupation of the endothelial ETB receptor leads to the production of NO, so that the ETA-induced vasoconstriction is partly reversed. ET-1 production is stimulated by angiotensin II, antidiuretic hormone (ADH), thrombin, cytokines, oxygen radicals, and shear stress on endothelial cells. ET-1 release is also stimulated by endotoxin, which may explain the elevated levels in patients with sepsis [65]. ET-1 release is inhibited by NO, prostacyclin, and atrial natriuretic peptide.
Selexipag for the treatment of pulmonary arterial hypertension
Published in Expert Review of Respiratory Medicine, 2021
Léon Genecand, Julie Wacker, Maurice Beghetti, Frédéric Lador
For the large majority of PAH patients, pulmonary vasoreactivity testing is negative, CCB are not useful and pulmonary vasodilator therapies should be tried. Imbalance between vasoconstrictors (thromboxane, endothelin) and vasodilators (nitric oxide, prostacyclin (PGI2)) is one of the various and complex physiopathological mechanism that leads to the development of PAH. Pulmonary vasodilators target three different pathways: 1) NO, 2) endothelin and 3) PGI2 [6]. NO is a pulmonary vasodilator that can be increased with phosphodiesterase-5 (PDE-5) inhibitors (sildenafil, tadalafil, and verdenafil) or guanylate cyclase stimulators (GCs) (riociguat). Endothelin is a pulmonary vasoconstrictor with mitogenic effects. Endothelin antagonists (bosentan, ambrisentan, macitentan) inhibit endogenous endothelin’s effects resulting in pulmonary vasodilatation. PGI2 have vasodilator, antiplatelet, and antiproliferative properties [7]. Synthetic PGI2 (Intravenous (IV) epoprostenol), PGI2 analogs (beraprost, iloprost, treprostinil), and PGI2 receptor agonist (selexipag) mimic the action of endogenous PGI2.
Related Knowledge Centers
- Clinical Research
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- Receptor
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