UBC Theses and Dissertations
Evaluation of Guinea pig models of the acute phase of allergic rhinitis AL Suleimani, Yousuf Mohammed
Allergic rhinitis is an allergen-IgE complex mediated inflammation of the nasal mucosa characterized by the symptoms of sneezing, nasal itchiness, rhinorrhea, and nasal congestion. The economical and social impact of allergic rhinitis is substantial. The effectiveness of currently available medications is limited. Investigation of more effective medications with fewer side effects is essential. Therefore, this study was intended to establish a model of allergic rhinitis in guinea pigs that can be utilized for further investigation of new medications. Furthermore, this study was also aimed to systematically evaluate the role of some inflammatory mediators of acute allergic reactions in guinea pigs in vivo. Male Dunkin Hartley guinea pigs were intranasally sensitized to, and challenged with, ovalbumin. Sneezing (SN) and nose rubbing (NR) were evaluated on day 21 post initiation of sensitization dose. From day 23 after first sensitization, the animals were anaesthetized with intraperitoneal pentobarbital (30-35mg/kg). The trachea was cannulated in both directions, caudally for measurement of nasal airway pressure (NAP) using a ventilator flow method (8ml/beat, 72beats/min) and rostrally for measurement of lung inflation pressure (LIP). Drugs were administered prior to ovalbumin challenge. SN and NR were evaluated for 30 minutes and NAP was evaluated within 30 minutes post challenge. Cellular infiltration (CI) was assessed from nasal lavage collected 60 minutes post challenge. Sensitized guinea pigs produced symptoms of SN, NR and nasal blockade (NB) in addition to eosinophil infiltration following ovalbumin challenge. A first generation H1 antihistamine, mepyramine, inhibited SN only, whereas later H1 antihistamine, cetirizine, inhibited SN, NR and NB. Montelukast, a leukotriene D4 receptor antagonist, and heparin prevented NB and CI. L-NAME , a non specific nitric oxide synthase inhibitor, inhibited NB and stimulated neutrophil infiltration. In non-sensitized guinea pigs, histamine and acetylcholine introduced intravenously caused dose-dependent decreases in NAP (by the action of histamine on H1 , M2 and perhaps M5 receptors, and acetylcholine on Ml receptors) and increases in LIP (by the action of histamine on H1 receptors, and acetylcholine on Ml receptors). In conclusion pathophysiological changes due to allergic rhinitis in guinea pigs resemble to some extent those in humans. The models reported here reflect the effectiveness of some drugs currently used to treat allergic rhinitis. The models can be used in investigating new potential drugs for the treatment of allergic rhinitis.
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