Characterization of nasal obstruction in the allergic XXXX using the forced oscillation method.

@entity8403 @entity840 @entity8765 @entity112 @entity17567
INTRODUCTION: This is the first report to evaluate changes in nasal resistance in a preclinical animal model using the forced oscillation method. METHODS: The method involves characterizing pressure-flow relationships of the respiratory system due to external oscillatory forces. RESULTS: First, we evaluated changes in nasal resistance using an established small-animal rhinometric technique. In these studies, aerosolized ovalbumin (3%) administered to the nasal cavity of ovalbumin-sensitized @entity840 increased nasal resistance at 30 min by 99 +/- 14%. The @entity112 H1 antagonists, @entity17567 (1 mg/kg i.v.) and @entity8765 (1 mg/kg i.v.), blocked the increase in nasal resistance due to ovalbumin provocation (50 +/- 17% and 39 +/- 11% over baseline, respectively). The alpha-adrenergic agonist @entity8403 (3 mg/ kg i.v.) had no effect on the nasal actions of ovalbumin. In separate studies, nasal resistance was measured at 2 Hz by forced oscillation and ovalbumin (3%) increased nasal resistance by 91 +/- 14%. @entity17567 (1 mg/kg i.v.) significantly attenuated the increase in nasal resistance due to ovalbumin. Finally, changes in nasal resistance for each treatment group were evaluated at frequencies of 1 - 18 Hz. Area under the curve analysis demonstrated that @entity17567 blocked the nasal obstructive effect of ovalbumin. In contrast, a pharmacologically active dose of @entity8403 (3 mg/kg i.v.) did not produce decongestant activity. DISCUSSION: The current data are inconsistent with the well-established clinical efficacy of alpha-adrenergic agonists as nasal decongestants. Consequently, we suggest that allergic nasal obstruction in the @entity840 may not be the best preclinical approach to assess the nasal decongestant activity of vasoconstrictor alpha-adrenergic agonists. Additionally, our studies demonstrate the utility of the forced oscillation technique in assessing changes in nasal resistance in small laboratory animals.
