ETB receptor-mediated vasodilation is regulated by estradiol in young women

2021 ◽  
Vol 321 (3) ◽  
pp. H592-H598
Author(s):  
Leena N. Shoemaker ◽  
Katherine M. Haigh ◽  
Andrew V. Kuczmarski ◽  
Shane J. McGinty ◽  
Laura M. Welti ◽  
...  
Keyword(s):  
Young Women ◽  
Gnrh Antagonist ◽  
Endogenous Hormone ◽  
Etb Receptor ◽  
Endothelin B

The endothelin-B (ETB) receptor mediates vasodilation in young women, an effect lost following menopause. It is unclear whether these alterations are due to aging or changes in estradiol (E2). During endogenous hormone suppression (GnRH antagonist), blockade of ETB receptors enhanced cutaneous microvascular vasodilation. However, during E2 administration, blockade of ETB receptors attenuated vasodilation, indicating that the ETB receptor mediates dilation in the presence of E2. In young women, ETB receptors mediate vasodilation in the presence of E2, an effect that is lost when E2 is suppressed.

Abstract P156: Estrogen Regulation of Endothelin-B Receptor Mediated Vasodilation

Hypertension ◽  
2017 ◽  
Vol 70 (suppl_1) ◽  
Author(s):  
Katherine Haigh ◽  
Ronald F Feinberg ◽  
Hugh S Taylor ◽  
Megan M Wenner
Keyword(s):  
Postmenopausal Women ◽  
Young Women ◽  
Local Heating ◽  
Receptor Blockade ◽  
Ovarian Hormone ◽  
Hormone Production ◽  
Doppler Flowmetry ◽  
Arterial Blood ◽  
Etb Receptor ◽  
Endothelin B

Our laboratory has recently demonstrated that a loss of endothelin-B (ETB) receptor mediated dilation contributes to impaired vasodilatory function in postmenopausal women. It is unclear if these changes are due to aging, or alterations in ovarian hormones that occur after menopause. The purpose of this study was to test the hypothesis that in a low estradiol state, there is a loss of ETB mediated dilation, and that estradiol administration reverses these responses and mediates dilation. Methods: We tested 8 young women (YW: 24±2 years, 23±1 kg/m 2 , mean arterial BP 84±2mHg) and 6 postmenopausal women (PMW: 56±1 years, 24±1 kg/m 2 , mean arterial BP 94±2mHg). In YW, we suppressed endogenous ovarian hormone production with daily gonadotropin-releasing hormone antagonist (GnRHant; Ganirelix) administration for 10 days, adding estradiol (E2, 0.1 mg/day, Vivelle dot patch) on days 4-10. PMW were tested at baseline and after 1-week E2 administration (0.1 mg/day, Vivelle dot patch). We measured nitric-oxide mediated vasodilation in the cutaneous circulation during local heating (42°C) via laser Doppler flowmetry, followed by microdialysis perfusions of sodium nitroprusside (28mM) with local heating to 43°C to elicit maximal dilation. Cutaneous vascular conductance (CVC) was calculated as cutaneous blood flow/mean arterial blood pressure, and expressed as a percent of maximal dilation. Results: ETB receptor blockade increased vasodilation in YW during hormone suppression with GnRHant (control: 88±3 vs. BQ-788: 94±2 CVC %max, P <0.05). However, ETB receptor blockaded tended to reduce vaodilation during E2 administration (control: 88±3 vs. BQ-788: 82±2 CVC %max, P =0.12). In PMW, ETB receptor blockade had no significant effect on vasodilatory responses (control: 90±4 vs. BQ-788: 95±2 CVC %max, P =0.20). Similarly, ETB receptor blockade did not alter vasodilation after E2 administration (control: 88±7 vs. BQ-788: 88±4 CVC %max). Conclusions: These preliminary data suggest that suppression of endogenous ovarian hormone production alters ETB receptor responses in young women, which is partially mediated by E2. Additional data are needed to determine ETB receptor sensitivity to E2 after menopause.

scholarly journals Endothelin ETB Receptor-Mediated Astrocytic Activation: Pathological Roles in Brain Disorders

2021 ◽  
Vol 22 (9) ◽  
pp. 4333
Author(s):  
Yutaka Koyama
Keyword(s):  
Traumatic Brain Injury ◽  
Brain Injury ◽  
Neurotrophic Factors ◽  
Drug Target ◽  
Therapeutic Strategy ◽  
Reactive Astrocytes ◽  
Brain Disorders ◽  
Etb Receptor ◽  
Target Molecules ◽  
Endothelin B

In brain disorders, reactive astrocytes, which are characterized by hypertrophy of the cell body and proliferative properties, are commonly observed. As reactive astrocytes are involved in the pathogenesis of several brain disorders, the control of astrocytic function has been proposed as a therapeutic strategy, and target molecules to effectively control astrocytic functions have been investigated. The production of brain endothelin-1 (ET-1), which increases in brain disorders, is involved in the pathophysiological response of the nervous system. Endothelin B (ETB) receptors are highly expressed in reactive astrocytes and are upregulated by brain injury. Activation of astrocyte ETB receptors promotes the induction of reactive astrocytes. In addition, the production of various astrocyte-derived factors, including neurotrophic factors and vascular permeability regulators, is regulated by ETB receptors. In animal models of Alzheimer’s disease, brain ischemia, neuropathic pain, and traumatic brain injury, ETB-receptor-mediated regulation of astrocytic activation has been reported to improve brain disorders. Therefore, the astrocytic ETB receptor is expected to be a promising drug target to improve several brain disorders. This article reviews the roles of ETB receptors in astrocytic activation and discusses its possible applications in the treatment of brain disorders.

Evidence for the existence of endothelin-B receptor subtypes and their physiological roles in the rat

1996 ◽  
Vol 271 (1) ◽  
pp. R254-R261 ◽  
Author(s):  
M. Gellai ◽  
T. Fletcher ◽  
M. Pullen ◽  
P. Nambi
Keyword(s):  
Radioligand Binding ◽  
Rat Kidney ◽  
Receptor Subtypes ◽  
Sprague Dawley ◽  
Vascular Effects ◽  
Renal Vasoconstriction ◽  
Eta Receptor ◽  
Etb Receptor ◽  
Endothelin B

The physiological roles of endothelin-B (ETB) receptor subtypes in systemic and renal hemodynamics were assessed in conscious Sprague-Dawley rats. Mean arterial pressure, hindlimb flow, and renal blood flow were measured via an implanted catheter and pulsed Doppler flow probes. Bolus intravenous injections of sarafotoxin 6c (S6c), a selective ETB agonist, elicited transient dose-dependent vasodilation, followed by sustained vasoconstriction in the systemic bed, but only vasoconstriction in the renal bed. RES-701-1, a selective ETB antagonist, blocked the dilator and potentiated the constrictor effect; SB-209670, a mixed ET receptor antagonist, attenuated both responses to S6c. In follow-up studies, the role of endogenous ET was assessed by administration of the antagonists alone: RES-701-1, SB-209670, and the ETA-selective antagonist BQ-123. RES-701-1 unmasked a significant systemic and renal vasoconstriction, which was attenuated by SB-209670 but not by BQ-123. SB-209670 and BQ-123 had no effect on basal hemodynamic parameters. Data from radioligand binding experiments showed that RES-701-1 binds with high affinity to the cloned human ETB receptor but poorly to the ETB receptor predominant in the rat kidney. Collectively, the results indicate that 1) the vascular effects of ET in the rat are mediated by two ETB receptor subtypes: an RES-701-1-sensitive subtype, mediating vasodilation, and an RES-701-1-insensitive subtype, mediating vasoconstriction; 2) the predominant role of endogenous ET is vasodilation; and 3) the ETA receptor plays a negligible role in the control of vascular tone in the rat.

scholarly journals Collecting duct-specific endothelin B receptor knockout increases ENaC activity

2012 ◽  
Vol 302 (1) ◽  
pp. C188-C194 ◽  
Author(s):  
Vladislav Bugaj ◽  
Elena Mironova ◽  
Donald E. Kohan ◽  
James D. Stockand
Keyword(s):  
Blood Pressure ◽  
Collecting Duct ◽  
Endothelin Receptors ◽  
Sodium Retention ◽  
Wild Type ◽  
Open Probability ◽  
Endothelin System ◽  
Etb Receptor ◽  
Endothelin B ◽  
Patch Clamp Electrophysiology

Collecting duct (CD)-derived endothelin-1 (ET-1) acting via endothelin B (ETB) receptors promotes Na+ excretion. Compromise of ET-1 signaling or ETB receptors in the CD cause sodium retention and increase blood pressure. Activity of the epithelial Na+ channel (ENaC) is limiting for Na+ reabsorption in the CD. To test for ETB receptor regulation of ENaC, we combined patch-clamp electrophysiology with CD-specific knockout (KO) of endothelin receptors. We also tested how ET-1 signaling via specific endothelin receptors influences ENaC activity under differing dietary Na+ regimens. ET-1 significantly decreased ENaC open probability in CD isolated from wild-type (WT) and CD ETA KO mice but not CD ETB KO and CD ETA/B KO mice. ENaC activity in WT and CD ETA but not CD ETB and CD ETA/B KO mice was inversely related to dietary Na+ intake. ENaC activity in CD ETB and CD ETA/B KO mice tended to be elevated under all dietary Na+ regimens compared with WT and CD ETA KO mice, reaching significance with high (2%) Na+ feeding. These results show that the bulk of ET-1 inhibition of ENaC activity is mediated by the ETB receptor. In addition, they could explain the Na+ retention and elevated blood pressure observed in CD ET-1 KO, CD ETB KO, and CD ETA/B KO mice consistent with ENaC regulation by ET-1 via ETB receptors contributing to the antihypertensive and natriuretic effects of the local endothelin system in the mammalian CD.

scholarly journals ETB Receptor Function is Modulated by Estradiol in Young Women

2020 ◽  
Vol 34 (S1) ◽  
pp. 1-1
Author(s):  
Leena N. Shoemaker ◽  
Katherine M. Haigh ◽  
Andrew V. Kuczmarski ◽  
Shane J. McGinty ◽  
Laura M. Welti ◽  
...  
Keyword(s):  
Young Women ◽  
Receptor Function ◽  
Etb Receptor

scholarly journals Topical Administration of Bosentan Prevents Retinal Neurodegeneration in Experimental Diabetes

2018 ◽  
Vol 19 (11) ◽  
pp. 3578 ◽  
Author(s):  
Patricia Bogdanov ◽  
Olga Simó-Servat ◽  
Joel Sampedro ◽  
Cristina Solà-Adell ◽  
Marta Garcia-Ramírez ◽  
...  
Keyword(s):  
Pharmacokinetic Study ◽  
Experimental Diabetes ◽  
Topical Administration ◽  
Control Group ◽  
Endothelin Receptor ◽  
Tunel Method ◽  
Diabetic Retina ◽  
Etb Receptor ◽  
Retinal Neurodegeneration ◽  
Endothelin B

Experimental evidence suggests that endothelin 1 (ET-1) is involved in the development of retinal microvascular abnormalities induced by diabetes. The effects of ET-1 are mediated by endothelin A- and B-receptors (ETA and ETB). Endothelin B-receptors activation mediates retinal neurodegeneration but there are no data regarding the effectiveness of ETB receptor blockage in arresting retinal neurodegeneration induced by diabetes. The main aim of the present study was to assess the usefulness of topical administration of bosentan (a dual endothelin receptor antagonist) in preventing retinal neurodegeneration in diabetic (db/db) mice. For this purpose, db/db mice aged 10 weeks were treated with one drop of bosentan (5 mg/mL, n = 6) or vehicle (n = 6) administered twice daily for 14 days. Six non-diabetic (db/+) mice matched by age were included as the control group. Glial activation was evaluated by immunofluorescence using specific antibodies against glial fibrillary acidic protein (GFAP). Apoptosis was assessed by TUNEL method. A pharmacokinetic study was performed in rabbits. We found that topical administration of bosentan resulted in a significant decrease of reactive gliosis and apoptosis. The results of the pharmacokinetic study suggested that bosentan reached the retina through the trans-scleral route. We conclude that topical administration of bosentan was effective in preventing neurodegeneration in the diabetic retina and, therefore, could be a good candidate to be tested in clinical trials.

scholarly journals Involvement of AP-1 and C/EBPβ in Upregulation of Endothelin B (ETB) Receptor Expression in a Rodent Model of Glaucoma

PLoS ONE ◽  
2013 ◽  
Vol 8 (11) ◽  
pp. e79183 ◽  
Author(s):  
Shaoqing He ◽  
Alena Z. Minton ◽  
Hai-Ying Ma ◽  
Dorota L. Stankowska ◽  
Xiangle Sun ◽  
...  
Keyword(s):  
Rodent Model ◽  
Receptor Expression ◽  
Etb Receptor ◽  
Endothelin B

Collecting duct-specific knockout of the endothelin B receptor causes hypertension and sodium retention

2006 ◽  
Vol 291 (6) ◽  
pp. F1274-F1280 ◽  
Author(s):  
Yuqiang Ge ◽  
Alan Bagnall ◽  
Peter K. Stricklett ◽  
Kevin Strait ◽  
David J. Webb ◽  
...  
Keyword(s):  
Collecting Duct ◽  
Receptor Gene ◽  
Plasma Renin ◽  
High Salt ◽  
Paracrine Effects ◽  
High Sodium ◽  
Eta Receptor ◽  
Etb Receptor ◽  
Endothelin B

Collecting duct (CD)-derived endothelin-1 (ET-1) inhibits renal Na reabsorption and its deficiency increases blood pressure (BP). The role of CD endothelin B (ETB) receptors in mediating these effects is unknown. CD-specific knockout of the ETB receptor was achieved using an aquaporin-2 promoter-Cre recombinase transgene and the loxP-flanked ETB receptor gene (CD ETB KO). Systolic BP in mice with CD-specific knockout of the ETB receptor, ETA receptor (CD ETA KO) and ET-1 (CD ET-1 KO), and their respective controls were compared during normal- and high-salt diet. On a normal-sodium diet, CD ETB KO mice had elevated BP, which increased further during high salt feeding. However, the degree of hypertension in CD ETB KO mice and the further increase in BP during salt feeding were lower than that of CD ET-1 KO mice, whereas CD ETA KO mice were normotensive. CD ETB KO mice had impaired sodium excretion following acute sodium loading. Aldosterone and plasma renin activity were decreased in CD ETB KO mice on normal- and high-sodium diets, while plasma and urinary ET-1 levels did not differ from controls. In conclusion, the CD ETB receptor partially mediates the antihypertensive and natriuretic effects of ET-1. CD ETA and ETB receptors do not fully account for the antihypertensive and natriuretic effects of CD-derived ET-1, suggesting paracrine effects of this peptide.

Sign in / Sign up

Export Citation Format

Share Document