title: Deterioration of epithelium mediated mechanisms in diabetic-antigen sensitized airways of guinea pigs.
abstract: The onset of diabetes causes disruption of respiratory epithelial mediators. The present study investigates whether diabetes modifies the epithelium mediated bronchial responses in hyper-reactive airway smooth muscle (ASM) primarily through nitric oxide (NO), cyclooxygenase (COX), and epithelium derived hyperpolarizing factor (EpDHF) pathways.
  
  
  
  Experimental model of guinea pigs having hyper-reactive airways with or without diabetes were developed. The responses of tracheal rings to cumulative concentrations of acetylcholine (ACh) and isoproterenol (IP) in the presence and absence of epithelium and before and after incubation with NO, K+ATPand COX inhibitors, N-(ω)-Nitro-L-arginine methyl ester (L-NAME; 100 μM), glybenclamide (10 μM) and indomethacin (100 μM) were assessed.
  
  
  
  In diabetic guinea pigs with hyper-reactive airways, a decrease in ACh induced bronchoconstriction was observed after epithelium removal and after incubation with L-NAME/indomethacin, suggesting damage to NO/COX pathways. Hyper-reactivity did not alter the response of trachea to ACh but affected the response to IP which was further reduced in hyper-reactive animals with diabetes. The ASM response to IP after glybenclamide treatment did not alter in hyper-reactive guinea pigs and diabetic guinea pigs with hyper-reactive airways, suggesting damage to the EpDHF pathway. Treatment with indomethacin reduced IP response in the hyper-reactive model, and did not produce any change in diabetic model with hyper-reactive airways, indicating further disruption of the COX pathway.
  
  
  
  EpDHF pathway is damaged in hyper-reactive guinea pigs and in diabetic guinea pigs with hyper-reactive airways. Diabetes further aggravates the NO and COX mediated pathways in diabetic guinea pigs with hyper-reactive airways.
authors.affiliation: Department of Physiology, VP Chest Institute, University of Delhi, Delhi, India.
authors.forename: Saidullah
authors.initials: S
authors.lastname: Bano
authors.forename: Omanwar
authors.initials: O
authors.lastname: Swati
authors.forename: Muralidhar
authors.initials: M
authors.lastname: Kambadur
authors.forename: Fahim
authors.initials: F
authors.lastname: Mohammad
mesh_terms: D000109:Acetylcholine / Q000276:immunology; D000818:Animals; D000942:Antigens, Bacterial; D001426:Bacterial Proteins; D016535:Bronchial Hyperreactivity / Q000276:immunology* / Q000473:pathology*; D016084:Bronchoconstriction / Q000276:immunology; D048909:Diabetes Complications / Q000276:immunology* / Q000473:pathology*; D003921:Diabetes Mellitus, Experimental / Q000276:immunology* / Q000473:pathology*; D005260:Female; D005905:Glyburide / Q000494:pharmacology; D006168:Guinea Pigs; D006801:Humans; D007213:Indomethacin / Q000494:pharmacology; D007545:Isoproterenol / Q000276:immunology; D008297:Male; D009130:Muscle, Smooth / Q000276:immunology / Q000473:pathology; D009569:Nitric Oxide; D011451:Prostaglandin-Endoperoxide Synthases; D020545:Respiratory Mucosa / Q000276:immunology* / Q000473:pathology*; D013311:Streptozocin; D014132:Trachea / Q000276:immunology* / Q000473:pathology*
chemical_list: D000942:Antigens, Bacterial; D001426:Bacterial Proteins; C093537:invJ protein, Salmonella typhimurium; D009569:Nitric Oxide; D013311:Streptozocin; D011451:Prostaglandin-Endoperoxide Synthases; D007545:Isoproterenol; D000109:Acetylcholine; D005905:Glyburide; D007213:Indomethacin