Mechanism of thromboxane receptor-induced vasoconstriction in human saphenous vein.

Autor: Ozen G; Department of Pharmacology, Faculty of Pharmacy, Istanbul University, Istanbul 34116, Turkey. Electronic address: gulsevozen@istanbul.edu.tr., Aljesri K; Department of Pharmacology, Faculty of Pharmacy, Istanbul University, Istanbul 34116, Turkey., Celik Z; Department of Pharmacology, Faculty of Pharmacy, Istanbul University, Istanbul 34116, Turkey., Turkyılmaz G; Department of Cardiovascular Surgery, Bakirkoy Dr Sadi Konuk Education and Research Hospital Bakırkoy, Istanbul, Turkey., Turkyılmaz S; Department of Cardiovascular Surgery, Bakirkoy Dr Sadi Konuk Education and Research Hospital Bakırkoy, Istanbul, Turkey., Teskin O; Department of Cardiovascular Surgery, Biruni University, Istanbul, Turkey., Norel X; Université de Paris, INSERM, UMR-S 1148, CHU X. Bichat, 75018 Paris, France., Topal G; Department of Pharmacology, Faculty of Pharmacy, Istanbul University, Istanbul 34116, Turkey.
Jazyk: angličtina
Zdroj: Prostaglandins & other lipid mediators [Prostaglandins Other Lipid Mediat] 2020 Dec; Vol. 151, pp. 106476. Date of Electronic Publication: 2020 Jul 25.
DOI: 10.1016/j.prostaglandins.2020.106476
Abstrakt: Saphenous vein (SV) is one of the most widely used graft material in patients undergoing coronary artery bypass graft surgery (CABG). Thromboxane A 2 (TXA 2 ) is implicated in graft failure by inducing vasoconstriction and platelet aggregation. The aim of this study is to investigate the mechanism involved in TXA 2 -induced vasoconstriction in human SV. The role of different inhibitors and blockers on U46619 (TXA 2 -mimetic)-induced vasoconstriction is investigated by using an isolated organ bath system. Relaxation responses to several mediators are evaluated in SV pre-contracted with U46619 and compared with those pre-contracted with phenylephrine. Our results demonstrate that U46619-induced contraction is completely blocked by myosin light chain kinase inhibitor ML-9 or TP receptor antagonist BAY u3405. Furthermore, U46619-induced contraction is partially inhibited by phospholipase C inhibitor U73122, protein kinase C inhibitor calphostin C, Rho-kinase inhibitor Y-27632, L-type calcium channel blocker nifedipine, store-operated channel inhibitor SKF96365 or removal of extracellular calcium. Relaxation responses to NO donor (sodium nitroprusside), guanylate cyclase (GC) stimulator (riociguat), phosphodiesterase (PDE) inhibitors (sildenafil, IBMX), adenylate cyclase (AC) activator (forskolin) and acetylcholine (ACh) are markedly reduced when U46619 is used as a pre-contraction agent. Our results demonstrate that influx of extracellular Ca 2+ (through L-type calcium channels and store-operated calcium channels) and intracellular Ca 2+ release together with Ca 2+ sensitization (through Rho-kinase activation) are necessary components for TXA 2 -induced vasoconstriction in SV. Moreover, more pronounced decrease in vasorelaxation induced by several mediators (SNP, riociguat, sildenafil, IBMX, forskolin, and ACh) in the presence of U46619 when compared with phenylephrine suggests that there is a crosstalk between the TP receptor signaling pathway and PDE, AC, GC enzymes. We believe that the investigation of mechanism of the TXA 2 -induced vasoconstriction in SV will provide additional information for the prevention of SV graft failure.
(Copyright © 2020 Elsevier Inc. All rights reserved.)
Databáze: MEDLINE
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