Characterization of nasal obstruction in the allergic guinea pig using the forced oscillation method

Abstract 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 guinea pigs increased nasal resistance at 30 min by 99±14%. The histamine H 1 antagonists, chlorpheniramine (1 mg/kg iv) and pyrilamine (1 mg/kg iv), blocked the increase in nasal resistance due to ovalbumin provocation (50±17% and 39±11% over baseline, respectively). The α-adrenergic agonist phenylpropanolamine (3 mg/kg iv) 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%. Chlorpheniramine (1 mg/kg iv) 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 chlorpheniramine blocked the nasal obstructive effect of ovalbumin. In contrast, a pharmacologically active dose of phenylpropanolamine (3 mg/kg iv) did not produce decongestant activity. Discussion: The current data are inconsistent with the well-established clinical efficacy of α-adrenergic agonists as nasal decongestants. Consequently, we suggest that allergic nasal obstruction in the guinea pig may not be the best preclinical approach to assess the nasal decongestant activity of vasoconstrictor α-adrenergic agonists. Additionally, our studies demonstrate the utility of the forced oscillation technique in assessing changes in nasal resistance in small laboratory animals.