EC Pharmacology And Toxicology

Bronchial asthma is an obstructive airway disease characterized by airway inflammation, and hyperresponsiveness to a variety of stimuli and airflow obstruction resulting in variable respiratory symptoms viz. cough, wheezing and shortness of breath. The pathophysiology of asthma involves the complex interactions among inflammatory cells, cytokines and mediators of stress. Nitric oxide (NO), initially identified as a vascular endothelial regulator, is being implicated for its role in obstructive airway diseases. The study was planned to evaluate the effects of NO modulators on ovalbumin (OVA) induced bronchial hyperresponsiveness, airflow resistance and airway inflammation in rats. Asthma was experimentally induced in rats by Ovalbumin (OVA) immunization (day 0) followed by OVA aerosol challenge (from day 8 to day 15) for 20 min, on each day. In this disease model, bronchial hyperrespon- siveness, airway inflammation and airflow restriction was classically expressed and served as the disease control (DC). All drugs (L-arginine, ABH, and prednisolone) were administered 30 minutes prior to aerosol challenge, daily for 8 days. To assess pulmonary function, 24 hours after the last OVA challenge, baseline p-enh, a marker of airway resistance and hyperresponsiveness was assessed in response to increasing doses of methacholine (spasmogen) aerosol using whole-body plethysmography. Following this, blood and BAL fluid samples were collected from different treatment groups and assayed for biomarkers of airway inflammation and oxidative stress. The results showed that in OVA immunized and challenged rats (DC), there was marked increase in p-enh values as compared to normal controls. Pre-treatment with both NO precursor, L-arginine, as well as arginase inhibitor, ABH, attenuated the raised p-enh values seen in the DC group. Assay of BAL fluid showed that eosinophil counts and OVA specific IgE levels were differentially raised in the DC group and these were attenuated by L-arginine and ABH treatments, which were comparable to the standard drug, prednisolone. Further, oxidative stress markers, like MDA was elevated in DC rats, which was also attenuated after L-arginine and ABH treatments. Thus, it is inferred that NO may play a crucial regulatory role in the pathophysiology of bronchial asthma by regulating bronchial hyperresponsiveness and airway inflammation and that interactions with oxidative stress may be involved in these effects.

 Keywords: Bronchial Asthma; Airway Hyperresponsiveness; Airway Inflammation; Nitric Oxide; L-Arginine; Arginase Inhibitor

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