title: Effects of furosemide on allergic asthmatic responses in mice.
abstract: BACKGROUND
  The syndrome of allergic asthma features reversible bronchoconstriction, airway inflammation and hyperresponsiveness as well as airway remodelling, including goblet cell hyperplasia. Managing severe asthma is still a clinical challenge. Numerous studies report that furosemide, an inhibitor of Na(+)-K(+)-Cl(-) cotransporter (NKCC) reduces airway hyperresponsiveness (AHR) in asthmatic patients. However, the mechanism by which furosemide exerts anti-asthmatic action remains unclear.
  
  
  OBJECTIVE
  This study sought to investigate the cellular profile of NKCC1 expression in the lung and examine the effects of furosemide on several outcome measurements in a mouse model of allergic asthma.
  
  
  METHODS
  Mice were sensitized and challenged with ovalbumin (OVA). Before challenge, the OVA-sensitized mice were treated with furosemide (4.0 mg/kg/day, via daily intraperitoneal injection for 5 days). Outcome measurements in naïve, OVA-exposure, furosemide-treated naïve and furosemide-treated OVA-exposed mice included the slope of the relationship between inhaled methacholine (MCh) concentration and respiratory system resistance (Slope·R(RS)), bronchoalveolar lavage (BAL) cell counts and immunohistochemical and immunoblotting assays of lung tissues.
  
  
  RESULTS
  NKCC1 immunoreactivity was observed in airway epithelial cells (AECs) and alveolar type II (ATII) cells of the control mice. OVA exposure enhanced the expression of NKCC1 in AECs and ATII cells, and increased the infiltration of NKCC1-expressing T lymphocytes in the lung. NKCC1 immunoreactivity was not detected in the airway smooth muscle (ASM) cells. Furosemide treatment reduced the Slope·R(RS) in both naïve and OVA-exposed mice by about 50%. Furosemide treatment also increased T lymphocyte infiltration to the lung in OVA-exposed mice by approximately 53%, but had no effect on pulmonary goblet cell hyperplasia.
  
  
  CONCLUSIONS
  Furosemide decreases basal airway responsiveness, thereby reducing the extent of allergen-induced AHR. However, the same treatment also increases T lymphocytes infiltration in the course of allergic asthma. Further studies are necessary to address the usefulness of furosemide in the clinical treatment of asthma.
authors: Institute of Physiology, Medical College of Shandong University, Shandong, China.
authors: S
authors: S
authors: Wang
authors: Y-Y
authors: YY
authors: Xiang
authors: R
authors: R
authors: Ellis
authors: J
authors: J
authors: Wattie
authors: M
authors: M
authors: Feng
authors: M D
authors: MD
authors: Inman
authors: W-Y
authors: WY
authors: Lu
mesh_terms: D000485:Allergens / Q000276:immunology; D000818:Animals; D018927:Anti-Asthmatic Agents / Q000494:pharmacology / Q000627:therapeutic use*; D001249:Asthma / Q000188:drug therapy* / Q000276:immunology; D016535:Bronchial Hyperreactivity / Q000188:drug therapy* / Q000209:etiology; D001992:Bronchoalveolar Lavage Fluid / Q000276:immunology; D004195:Disease Models, Animal; D005665:Furosemide / Q000494:pharmacology / Q000627:therapeutic use*; D020397:Goblet Cells / Q000187:drug effects / Q000473:pathology; D006967:Hypersensitivity / Q000188:drug therapy* / Q000276:immunology; D008168:Lung / Q000276:immunology / Q000378:metabolism; D016210:Methacholine Chloride / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D010047:Ovalbumin / Q000008:administration & dosage / Q000276:immunology; D028021:Sodium-Potassium-Chloride Symporters / Q000378:metabolism; D064506:Solute Carrier Family 12, Member 2; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology*; D016896:Treatment Outcome
chemical_list: D000485:Allergens; D018927:Anti-Asthmatic Agents; C578878:Slc12a2 protein, mouse; D028021:Sodium-Potassium-Chloride Symporters; D064506:Solute Carrier Family 12, Member 2; D016210:Methacholine Chloride; D005665:Furosemide; D010047:Ovalbumin