Deterioration of epithelium mediated mechanisms in diabetic-antigen sensitized airways of guinea pigs

Autor: Muralidhar Kambadur, Saidullah Bano, Omanwar Swati, Fahim Mohammad
Jazyk: angličtina
Rok vydání: 2016
Předmět:
0301 basic medicine
Male
Physiology
Original
Indomethacin
chemistry.chemical_compound
Glyburide
Respiratory system
biology
diabetes
General Medicine
respiratory system
cycloxygenase pathway
Trachea
medicine.anatomical_structure
Bronchoconstriction
Female
medicine.symptom
Bronchial Hyperreactivity
Acetylcholine
medicine.drug
medicine.medical_specialty
Guinea Pigs
Respiratory Mucosa
Nitric Oxide
Streptozocin
Nitric oxide
NO
Diabetes Mellitus
Experimental
Diabetes Complications
03 medical and health sciences
Antigen
Bacterial Proteins
Diabetes mellitus
Internal medicine
medicine
Animals
Humans
Antigens
Bacterial
Isoproterenol
Muscle
Smooth
asthma
medicine.disease
Epithelium
030104 developmental biology
Endocrinology
chemistry
Prostaglandin-Endoperoxide Synthases
Immunology
biology.protein
K+ATP
Cyclooxygenase
epithelium
Zdroj: Journal of Smooth Muscle Research
ISSN: 1884-8796
0916-8737
Popis: BACKGROUND 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. METHODS 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+ATP and COX inhibitors, N-(ω)-Nitro-L-arginine methyl ester (L-NAME; 100 μM), glybenclamide (10 μM) and indomethacin (100 μM) were assessed. RESULTS 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. CONCLUSION 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.
Databáze: OpenAIRE
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