title: The influence of ETA and ETB receptor blockers on LPS-induced oxidative stress and NF-κB signaling pathway in heart.
abstract: The aim of this study was to assess whether an endothelin-A receptor (ETA-R) blocker, BQ123, or an endothelin-B (ETB-R) receptor blocker, BQ788, influences nuclear factor kappa beta (NF-κB) pathway, free radical generation, tumor necrosis factor-alpha (TNF-α) concentration, and glutathione redox system in hearts obtained from lipopolysaccharide (LPS)-induced endotoxic rats. The study was performed on rats divided into groups: 1) saline, 2) saline + LPS (15 mg/kg), 3) BQ123 (1 mg/kg b.w.) + LPS, 4) BQ123 (0.5 mg/kg b.w.) + LPS, 5) BQ788 (3 mg/kg b.w.) + LPS. The ETA-R and ETB-R antagonists were injected i.v. 30 min before LPS administration. In rats, BQ123 caused a significant decrease in TBARS (p < 0.05) but not in H2O2 concentration. It also decreased tissue protein level and improved tissue redox status (p < 0.01). Only a dose of 1 mg/kg decreased TNF-α concentration (p < 0.05). BQ788 lowered TBARS, H2O2 and protein concentration (p < 0.05; p < 0.02; p < 0.001, respectively), however, it did not affect TNF-α concentration. Neither ETA-R nor ETB-R blockers influenced LPS-induced increase in p65 subunit level and activation of NF-κB pathway. Our results demonstrated that ETA-R blockage is more effective in inhibiting free radical generation and improving heart antioxidant properties than ETB-R blockage under oxidative stress. NF-κB pathway is not incorporated in ETA-R and ETB-R influence on ROS production.
authors.affiliation: Department of Cardiovascular Physiology, Medical University of Lodz, Lodz, Poland. piechota.aleksandra@wp.pl
authors.forename: Aleksandra
authors.initials: A
authors.lastname: Piechota-Polanczyk
authors.forename: Paulina
authors.initials: P
authors.lastname: Kleniewska
authors.forename: Anna
authors.initials: A
authors.lastname: Gorąca
mesh_terms: D000818:Animals; D065130:Endothelin A Receptor Antagonists; D065131:Endothelin B Receptor Antagonists; D006321:Heart / Q000187:drug effects; D008070:Lipopolysaccharides / Q000494:pharmacology*; D008297:Male; D009206:Myocardium / Q000378:metabolism*; D016328:NF-kappa B / Q000378:metabolism*; D009842:Oligopeptides / Q000008:administration & dosage; D018384:Oxidative Stress / Q000187:drug effects / Q000502:physiology*; D010456:Peptides, Cyclic / Q000008:administration & dosage; D010880:Piperidines / Q000008:administration & dosage; D051381:Rats; D017208:Rats, Wistar; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology*
chemical_list: D065130:Endothelin A Receptor Antagonists; D065131:Endothelin B Receptor Antagonists; D008070:Lipopolysaccharides; D016328:NF-kappa B; D009842:Oligopeptides; D010456:Peptides, Cyclic; D010880:Piperidines; C086539:BQ 788; C072247:cyclo(Trp-Asp-Pro-Val-Leu)