Characterization of nasal obstruction in the allergic guinea pig using the forced oscillation method.
BACKGROUND
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 H1 antagonists, chlorpheniramine (1 mg/kg i.v.) and pyrilamine (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 phenylpropanolamine (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%. Chlorpheniramine (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 chlorpheniramine blocked the nasal obstructive effect of ovalbumin. In contrast, a pharmacologically active dose of phenylpropanolamine (3 mg/kg i.v.) did not produce decongestant activity.


CONCLUSIONS
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 guinea pig 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.
Department of Allergy, Schering-Plough Research Institute, 2015 Galloping Hill Road, Kenilworth, NJ 07033-0539, USA. robbie.mcleod@spcorp.com
Robbie L
RL
McLeod
Simon S
SS
Young
Christine H
CH
Erickson
Leonard E
LE
Parra
John A
JA
Hey
D000403:Airway Resistance / Q000187:drug effects; D000818:Animals; D018926:Anti-Allergic Agents / Q000627:therapeutic use; D002744:Chlorpheniramine / Q000627:therapeutic use; D004353:Drug Evaluation, Preclinical; D006168:Guinea Pigs; D006634:Histamine H1 Antagonists / Q000494:pharmacology* / Q000627:therapeutic use; D008297:Male; D014663:Nasal Decongestants / Q000494:pharmacology* / Q000627:therapeutic use; D015508:Nasal Obstruction / Q000139:chemically induced / Q000188:drug therapy* / Q000503:physiopathology; D009991:Oscillometry / Q000379:methods*; D010047:Ovalbumin / Q000494:pharmacology; D011738:Pyrilamine / Q000627:therapeutic use; D013997:Time Factors
D018926:Anti-Allergic Agents; D006634:Histamine H1 Antagonists; D014663:Nasal Decongestants; D002744:Chlorpheniramine; D010047:Ovalbumin; D011738:Pyrilamine