title: Effects of ketanserin on endotoxic shock and baroreflex function in rodents.
abstract: BACKGROUND
  Ketanserin, a 5-hydroxytryptamine receptor antagonist, is clinically used as an antihypertensive agent and could enhance baroreflex function. The present work tested the hypothesis that restoration of baroreflex function is an effective treatment for lipopolysaccharide (LPS)-induced shock.
  
  
  METHODS
  Kunming mice were injected with LPS (30 mg/kg; intraperitoneal) to induce endotoxic shock. Ketanserin (0.3, 1, 3, or 10 mg/kg; intraperitoneal) was administered immediately after LPS injection. Survival time was monitored, and serum cytokines were analyzed after the onset of LPS. Effects of ketanserin were also examined in IL-10-deficient mice and mice with sinoaortic denervation. Finally, effects of ketanserin on blood pressure, heart rate, and baroreflex sensitivity were examined in Wistar-Kyoto (WKY) rats with endotoxic shock.
  
  
  RESULTS
  Ketanserin significantly increased survival time and decreased serum levels of tumor necrosis factor α and interleukin (IL) 1β in mice with endotoxic shock. At a dose of 10 mg/kg, ketanserin also significantly increased serum IL-10 concentration. The antishock effect of ketanserin was also apparent in IL-10-knockout mice. In mice with sinoaortic denervation, however, ketanserin had little antishock effects. In WKY rats, ketanserin significantly prevented the baroreflex impairment induced by LPS and prolonged the survival time.
  
  
  CONCLUSIONS
  Ketanserin could ameliorate endotoxic shock by restoring baroreflex function.
authors.affiliation: Department of Pharmacology, Second Military Medical University, Shanghai, China.
authors.forename: Chong
authors.initials: C
authors.lastname: Liu
authors.forename: Gu-Fang
authors.initials: GF
authors.lastname: Zhang
authors.forename: Shu-Wei
authors.initials: SW
authors.lastname: Song
authors.forename: Guo-Jun
authors.initials: GJ
authors.lastname: Cai
authors.forename: Wen-Hao
authors.initials: WH
authors.lastname: Liu
authors.forename: Chao-Yu
authors.initials: CY
authors.lastname: Miao
authors.forename: Ding-Feng
authors.initials: DF
authors.lastname: Su
mesh_terms: D000818:Animals; D017704:Baroreflex / Q000187:drug effects*; D001794:Blood Pressure / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D006339:Heart Rate / Q000187:drug effects; D016753:Interleukin-10 / Q000097:blood; D053583:Interleukin-1beta / Q000097:blood; D007650:Ketanserin / Q000494:pharmacology* / Q000627:therapeutic use*; D008070:Lipopolysaccharides; D008297:Male; D051379:Mice; D051381:Rats; D011921:Rats, Inbred WKY; D012702:Serotonin Antagonists / Q000494:pharmacology* / Q000627:therapeutic use*; D012772:Shock, Septic / Q000097:blood / Q000139:chemically induced / Q000188:drug therapy*; D016019:Survival Analysis; D014409:Tumor Necrosis Factor-alpha / Q000097:blood
chemical_list: D053583:Interleukin-1beta; D008070:Lipopolysaccharides; D012702:Serotonin Antagonists; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10; D007650:Ketanserin