UCL Discovery
UCL home » Library Services » Electronic resources » UCL Discovery

20-hydroxyecdysone dilates muscle arterioles in a nitric oxide-dependent, estrogen ER-β receptor-independent manner

Orie, NN; Raees, A; Aljaber, MY; Mohamed-Ali, N; Bensmail, H; Hamza, MM; Al-Ansari, N; ... Almaadheed, M; + view all (2021) 20-hydroxyecdysone dilates muscle arterioles in a nitric oxide-dependent, estrogen ER-β receptor-independent manner. Phytomedicine Plus , 1 (3) , Article 100078. 10.1016/j.phyplu.2021.100078. Green open access

[thumbnail of 1-s2.0-S2667031321000609-main.pdf]
Preview
Text
1-s2.0-S2667031321000609-main.pdf - Published Version

Download (2MB) | Preview

Abstract

BACKGROUND: 20-hydroxyecdysone is an ecdysteroid which is abundant in plants and insects and has anabolic potentials in mammals. It was recently shown to have affinity for estrogen ER-β receptor, which could potentially make it vasodilatory. Yet this possibility has not been previously investigated. Such an activity in muscle arterioles could have huge implications for muscle blood flow and performance. HYPOTHESIS/PURPOSE: We hypothesized that 20-hydroxyecdysone would dilate muscle arterioles by activating estrogen ER-β receptors. To test this, we investigated its vasodilatory properties in ovine muscle arterioles and further explored the mechanisms in human tissues and cells. STUDY DESIGN: The study was carried out experimentally, employing functional recording of arteriolar reactivity in intact ovine muscle arterioles and gene and protein expression analysis in human tissues and cells. METHODS: Direct effects of the compound on arteriolar tone were assessed by wire myography in abdominal muscle and mesenteric arterioles isolated from samples obtained from male sheep. The roles of endothelial nitric oxide synthase (NOS3), cyclooxygenase (COX) and estrogen ER-β receptor (ER-β), and their effects were determined with specific blockers. The NOS3 mRNA and protein expressions were analyzed in human coronary artery endothelial cells (HCAECs) and humanized liver of uPA+/+-SCID mice, before and after 20-hydroxyecdysone administration. RESULTS: Comparable dose-dependent relaxations were recorded for 20-hydroxyecdysone in both muscle and mesenteric arterioles with maximum relaxations of 46.94 ± 5.84% and 56.88 ± 7.04% respectively, which were not statistically different. Similar relaxation was recorded for β-estradiol in both arterioles. NOS inhibition with 100 µM L-NAME attenuated the relaxation to 20-hydroxyecdysone (p < 0.001) and β-estradiol (p < 0.001) in muscle arterioles. Neither COX inhibition with 10 µM indomethacin nor ER blockade with 1 µM PHTPP or 1 µM ICI182780 had any noticeable effect on 20-hydroxyecdysone relaxation in these arterioles. Transcriptome analysis revealed elevated NOS3 gene in the humanized liver of 20-hydroxyecdysone-treated mice, and, elevation of both NOS3 mRNA and protein in HCAECs treated with 20-hydroxyecdysone. CONCLUSION: The data suggest that 20-hydroxyecdysone has a nitric oxide-dependent, but ERβ-independent, vasodilatory property in muscle arterioles. The benefits to muscle blood flow would however be dependent on the impact of its effects on other vascular beds.

Type: Article
Title: 20-hydroxyecdysone dilates muscle arterioles in a nitric oxide-dependent, estrogen ER-β receptor-independent manner
Open access status: An open access version is available from UCL Discovery
DOI: 10.1016/j.phyplu.2021.100078
Publisher version: https://doi.org/10.1016/j.phyplu.2021.100078
Language: English
Additional information: © 2021 The Authors. Published by Elsevier B.V. under a Creative Commons license (https://creativecommons.org/licenses/by-nc-nd/4.0/).
Keywords: 20-hydroxyecdysone, Vasodilation, Muscle arterioles, Nitric oxide synthase 3, Estrogen receptor ER-β
UCL classification: UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Medicine
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Medicine > Inflammation
URI: https://discovery.ucl.ac.uk/id/eprint/10151276
Downloads since deposit
0Downloads
Download activity - last month
Download activity - last 12 months
Downloads by country - last 12 months

Archive Staff Only

View Item View Item