Mechanism of thromboxane receptor-induced vasoconstriction in human saphenous vein

Ozen G., Aljesri K., Celik Z., Turkyılmaz G., Turkyılmaz S., Teskin O., ...Daha Fazla

PROSTAGLANDINS & OTHER LIPID MEDIATORS, cilt.151, 2020 (SCI-Expanded) identifier identifier identifier

  • Yayın Türü: Makale / Tam Makale
  • Cilt numarası: 151
  • Basım Tarihi: 2020
  • Doi Numarası: 10.1016/j.prostaglandins.2020.106476
  • Dergi Adı: PROSTAGLANDINS & OTHER LIPID MEDIATORS
  • Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Scopus, Academic Search Premier, BIOSIS, CAB Abstracts, Chemical Abstracts Core, EMBASE, MEDLINE, Veterinary Science Database
  • Anahtar Kelimeler: TXA(2), Human saphenous vein, Vasoconstriction, U46619, HUMAN INTERNAL MAMMARY, PROTEIN-KINASE-C, MUSCLE-CELLS INHIBITION, ARTERY-BYPASS-SURGERY, HUMAN VASCULAR-TONE, SMOOTH-MUSCLE, RADIAL ARTERY, NITRIC-OXIDE, RHO-KINASE, CARDIOPULMONARY BYPASS
  • İstanbul Üniversitesi Adresli: Evet

Özet

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 Ca2+ (through L-type calcium channels and storeoperated calcium channels) and intracellular Ca2+ release together with Ca2+ 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.