Onset of diabetes modulates the airway smooth muscle reactivity of guinea pigs: role of epithelial mediators.
BACKGROUND
Diabetes induces lung dysfunction, leading to alteration in the pulmonary functions. Our aim was to investigate whether the early stage of diabetes alters the epithelium-dependent bronchial responses and whether nitric oxide (NO), KATP channels and cyclooxygenase (COX) pathways contribute in this effect.


METHODS
Guinea pigs were treated with a single injection of streptozotocin (180 mg/kg, i.p.) for induction of diabetes. Airway conductivity was assessed by inhaled histamine, using a non-invasive body plethysmography. The contractile responses of tracheal rings induced by acetylcholine (ACh) and relaxant responses of precontracted rings, induced by isoproterenol (IP) were compared in the presence and absence of the epithelium. Effects of N(ω)-Nitro-L-arginine methyl ester (L-NAME, a nitric oxide synthase inhibitor), glybenclamide (a KATP channel inhibitor) and indomethacin (a COX inhibitor) were also assessed in diabetic guinea pigs.


RESULTS
Early stage diabetes did not alter the airway conductivity. ACh-induced bronchoconstriction in epithelium intact tracheal rings was not affected by the onset of diabetes, however a reduction in the increased ACh responses due to epithelium removal, to L-NAME or to indomethacin was observed. The relaxation response to IP was impaired in trachea from guinea pigs in which diabetes had just developed. Early diabetes significantly reduced the IP response to glybenclamide and to indomethacin.


CONCLUSIONS
Our results demonstrate that the early stage of diabetes, modulate the bronchial reactivity to both ACh and IP by disrupting the NO, KATP channels and COX pathways, without affecting the airway conductivity in guinea pigs.
Department of Physiology, VP Chest Institute, University of Delhi, Delhi , India.
Bano
B
Saidullah
Kambadur
K
Muralidhar
Mohammad
M
Fahim
D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D001980:Bronchi / Q000187:drug effects / Q000503:physiopathology*; D016084:Bronchoconstriction / Q000187:drug effects; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology; D003921:Diabetes Mellitus, Experimental / Q000503:physiopathology*; D005260:Female; D005905:Glyburide / Q000494:pharmacology; D006168:Guinea Pigs; D066298:In Vitro Techniques; D007213:Indomethacin / Q000494:pharmacology; D007545:Isoproterenol / Q000494:pharmacology; D054086:KATP Channels / Q000037:antagonists & inhibitors / Q000502:physiology; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects; D009130:Muscle, Smooth / Q000187:drug effects / Q000503:physiopathology*; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009569:Nitric Oxide / Q000037:antagonists & inhibitors / Q000502:physiology; D011451:Prostaglandin-Endoperoxide Synthases / Q000502:physiology; D020545:Respiratory Mucosa / Q000503:physiopathology*; D015398:Signal Transduction / Q000502:physiology; D013311:Streptozocin
D016861:Cyclooxygenase Inhibitors; D054086:KATP Channels; D009569:Nitric Oxide; D013311:Streptozocin; D011451:Prostaglandin-Endoperoxide Synthases; D007545:Isoproterenol; D000109:Acetylcholine; D005905:Glyburide; D019331:NG-Nitroarginine Methyl Ester; D007213:Indomethacin