title: Influence of specific endothelin-1 receptor blockers on hemodynamic parameters and antioxidant status of plasma in LPS-induced endotoxemia.
abstract: BACKGROUND
  The potent vasoconstrictor endothelin-1 has been implicated in the pathogenesis of plasma oxidative stress seen in sepsis. The selective endothelin receptor blockers BQ123 and BQ788 were used to investigate the importance of selective endothelin receptor blockage in modulating oxidative stress during endotoxemia.
  
  
  METHODS
  The study was performed on male Wistar rats (n = 6 per group) divided into groups: (1) saline, (2) lipopolysaccharide (LPS) (15 mg/kg)-saline, (3) BQ123 (0.5 mg/kg)-LPS, (4) BQ123 (1 mg/kg)-LPS, (5) BQ788 (3 mg/kg)-LPS. The endothelin receptor type A(ETA-R) or type B (ETB-R) antagonist was injected intravenously 30 min before LPS administration. Blood pressure was monitored and blood was taken before, 90 min and 300 min after saline or LPS administration.
  
  
  RESULTS
  Injection of LPS alone resulted in a decrease in mean arterial pressure (MAP) (p < 0.05), a decrease in ferric reducing ability of plasma (FRAP) value (p < 0.01) and a marked increase in plasma tumor necrosis factor α (TNF-α) and thiobarbituric acid reactive substances (TBARS) (p < 0.001, p < 0.001, respectively). Administration of BQ123 before LPS administration deteriorated MAP in a dose dependent way. Moreover, BQ123 (1 mg/kg) decreased plasma level of TBARS and TNF-α (p < 0.01 and p < 0.05, respectively) and increased FRAP value (p < 0.001). On the contrary, BQ788 prevented LPS-induced decrease in MAP(p < 0.001) and led to a significant reduction in plasma TBARS concentration (p < 0.01).
  
  
  CONCLUSIONS
  Our study showed that blockage of ETB-R during endotoxemia improved blood hemodynamics and decreased plasma lipid peroxidation. Blockage of ETA-R improved plasma antioxidant status and decreased lipid peroxidation and TNF-α production, but it deteriorated hemodynamic conditions.
authors: Chair of Experimental and Clinical Physiology, Department of Cardiovascular Physiology, Medical University of Lodz, Mazowiecka 6/8, PL 92-215 Łódź, Poland. piechota.aleksandra@wp.pl
authors: Aleksandra
authors: A
authors: Piechota-Polańczyk
authors: Anna
authors: A
authors: Gorąca
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000494:pharmacology; D062186:Arterial Pressure / Q000187:drug effects; D004195:Disease Models, Animal; D004334:Drug Administration Schedule; D065130:Endothelin A Receptor Antagonists; D065131:Endothelin B Receptor Antagonists; D019332:Endothelin-1 / Q000378:metabolism*; D019446:Endotoxemia / Q000097:blood / Q000139:chemically induced / Q000188:drug therapy* / Q000503:physiopathology; D006439:Hemodynamics / Q000187:drug effects*; D007275:Injections, Intravenous; D015227:Lipid Peroxidation / Q000187:drug effects; D008070:Lipopolysaccharides; D008297:Male; D009842:Oligopeptides / Q000008:administration & dosage / Q000494:pharmacology* / Q000633:toxicity; D018384:Oxidative Stress / Q000187:drug effects*; D010456:Peptides, Cyclic / Q000008:administration & dosage / Q000494:pharmacology* / Q000633:toxicity; D010880:Piperidines / Q000008:administration & dosage / Q000494:pharmacology* / Q000633:toxicity; D051381:Rats; D011921:Rats, Inbred WKY; D044022:Receptor, Endothelin A / Q000378:metabolism; D044023:Receptor, Endothelin B / Q000378:metabolism; D017392:Thiobarbituric Acid Reactive Substances / Q000378:metabolism; D013997:Time Factors; D014409:Tumor Necrosis Factor-alpha / Q000097:blood; D014662:Vasoconstrictor Agents / Q000494:pharmacology
chemical_list: D000975:Antioxidants; D065130:Endothelin A Receptor Antagonists; D065131:Endothelin B Receptor Antagonists; D019332:Endothelin-1; D008070:Lipopolysaccharides; D009842:Oligopeptides; D010456:Peptides, Cyclic; D010880:Piperidines; D044022:Receptor, Endothelin A; D044023:Receptor, Endothelin B; D017392:Thiobarbituric Acid Reactive Substances; D014409:Tumor Necrosis Factor-alpha; D014662:Vasoconstrictor Agents; C433788:lipopolysaccharide, E. coli O26-B6; C086539:BQ 788; C072247:cyclo(Trp-Asp-Pro-Val-Leu)