eprintid: 10113535 rev_number: 20 eprint_status: archive userid: 608 dir: disk0/10/11/35/35 datestamp: 2020-11-19 10:13:23 lastmod: 2020-11-19 10:13:23 status_changed: 2020-11-19 10:13:23 type: thesis metadata_visibility: show creators_name: Raees, Asmaa title: Microvascular endothelial dilator function: role of COX and the effects of ecdysteroids ispublished: unpub divisions: UCL divisions: A01 divisions: B02 divisions: C10 divisions: D17 note: Copyright © The Author 2020. Original content in this thesis is licensed under the terms of the Creative Commons Attribution 4.0 International (CC BY 4.0) Licence (https://creativecommons.org/licenses/by/4.0/). Any third-party copyright material present remains the property of its respective owner(s) and is licensed under its existing terms. Access may initially be restricted at the author’s request. abstract: Cyclooxygenase (COX), which can be expressed as COX-1 or COX-2 in endothelial cells has the unique ability to regulate microvascular tone through balanced production of dilator/constrictor prostanoids. This study investigated the roles of these isoforms in microvascular endothelial dilator function and how these are affected by supplement-derived ecdysteroids. Acetylcholine or 20-hydroxyecdysone relaxation were recorded in Skeletal muscle (SKM) and mesenteric (ME) arteries from healthy sheep and omental (OM) and subcutaneous (SC) fat arteries from obese humans by wire myography in the absence and presence of inhibitors of nitric oxide synthase, cyclooxygenase (COX) isoforms 1 and 2 and endothelium-derived hyperpolarizing factors. Gene and protein expression analysis were also carried out to fully characterize the roles of COX in these arteries. Non-selective COX inhibition attenuated acetylcholine relaxation in SKM arteries but enhanced it in ME arteries. Selective inhibition of COX-1 in both SKM and ME arteries also attenuated acetylcholine relaxation. In contrast, selective inhibition of COX-2 enhanced acetylcholine relaxation in ME arteries and had no effect in SKM arteries. In OM arteries from obese patients, selective inhibition of COX-1 but not COX-2 significantly improved acetylcholine relaxation. The OM arteries also displayed enhanced responsiveness to thromboxane A2 mimetic (U46619) compared with SC arteries. 20-hydroxyecdysone caused relaxation which was attenuated by NOS inhibition compared with COX inhibition in SKM and ME arteries. COX roles in microvascular endothelial dilator function are isoform-specific and dependent on type and health of the vasculature. In healthy arteries, COX-1 promotes but COX-2 opposes vasodilation. In human obesity, COX-1 opposes while COX plays no part in OM endothelial dilator function. Although 20-hydroxyecdysone alters COX expression, its vasodilatory effect is more eNOS-dependent than COX-dependent. date: 2020-10-28 date_type: published oa_status: green full_text_type: other thesis_class: doctoral_open thesis_award: Ph.D language: eng thesis_view: UCL_Thesis primo: open primo_central: open_green verified: verified_manual elements_id: 1825018 lyricists_name: Raees, Asmaa lyricists_id: ARAEE13 actors_name: Raees, Asmaa actors_name: Allington-Smith, Dominic actors_id: ARAEE13 actors_id: DAALL44 actors_role: owner actors_role: impersonator full_text_status: public pages: 214 event_title: UCL (University College London) institution: UCL (University College London) department: Division of Medicine thesis_type: Doctoral citation: Raees, Asmaa; (2020) Microvascular endothelial dilator function: role of COX and the effects of ecdysteroids. Doctoral thesis (Ph.D), UCL (University College London). Green open access document_url: https://discovery-pp.ucl.ac.uk/id/eprint/10113535/3/Raees_10113535_thesis.pdf