title: Novel anti-inflammatory effects of doxazosin in rodent models of inflammation.
abstract: BACKGROUND
  Doxazosin is an α(1)-adrenergic receptor antagonist for the treatment of high blood pressure and benign prostatic hyperplasia. Peripheral α-adrenergic receptors have been implicated in inflammation.
  
  
  OBJECTIVE
  To examine the anti-inflammatory effects of doxazosin in rodent models of inflammation.
  
  
  METHODS
  The anti-inflammatory properties of doxazosin were investigated in 4 models. In all studies, drug treatment was administered 15 min prior to challenge. In the lipopolysaccharide (LPS)-induced systemic inflammation model, LPS was injected systemically at 0.25 mg/kg. At 90 min after challenge, blood samples were collected for analysis. In the LPS-induced pulmonary inflammation model, LPS was instilled intranasally. Four hours after challenge, the lungs were harvested for monocyte chemoattractant protein-1 (MCP-1) analysis. In a delayed-type hypersensitivity model, the mice were injected intravenously with sheep red blood cells, and rechallenged in the left footpad 7 days later. Drug treatment was given on day 6 and 7 just prior to the rechallenge. The thickness of hind footpads was measured at 15 min after rechallenge. In the thioglycollate-induced peritoneal monocyte infiltration model, mice were challenged with 3% thioglycollate, and 2 h later peritoneal lavage fluid was collected for MCP-1 analysis.
  
  
  RESULTS
  In animals challenged systemically and intranasally with LPS, doxazosin inhibited TNF-α and MCP-1 production, respectively. In the delayed-type hypersensitivity model, footpad swelling was inhibited by doxazosin. Doxazosin decreased the level of MCP-1 release in the peritoneal cavity of thioglycollate-stimulated animals, though this effect was not statistically significant.
  
  
  CONCLUSIONS
  This is the first set of studies that reports the novel anti-inflammatory effects of doxazosin.
authors.affiliation: BioMed Valley Discoveries, Kansas City, MO 64111, USA. dtung@biomed-valley.com
authors.forename: David
authors.initials: D
authors.lastname: Tung
authors.forename: John
authors.initials: J
authors.lastname: Ciallella
authors.forename: Peter H
authors.initials: PH
authors.lastname: Cheung
authors.forename: Saurabh
authors.initials: S
authors.lastname: Saha
mesh_terms: D058668:Adrenergic alpha-1 Receptor Antagonists / Q000494:pharmacology / Q000627:therapeutic use*; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology / Q000627:therapeutic use*; D018932:Chemokine CCL2 / Q000276:immunology; D004195:Disease Models, Animal; D017292:Doxazosin / Q000494:pharmacology / Q000627:therapeutic use*; D004912:Erythrocytes / Q000276:immunology; D006968:Hypersensitivity, Delayed / Q000188:drug therapy* / Q000473:pathology; D007249:Inflammation / Q000139:chemically induced / Q000188:drug therapy* / Q000276:immunology; D008070:Lipopolysaccharides; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D010538:Peritonitis / Q000139:chemically induced / Q000188:drug therapy* / Q000276:immunology; D012756:Sheep; D013864:Thioglycolates; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology
chemical_list: D058668:Adrenergic alpha-1 Receptor Antagonists; D000893:Anti-Inflammatory Agents; C491768:Ccl2 protein, mouse; D018932:Chemokine CCL2; D008070:Lipopolysaccharides; D013864:Thioglycolates; D014409:Tumor Necrosis Factor-alpha; D017292:Doxazosin