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Abstract

Objective

To determine the effect of in vivo antigen sensitization (Ascaris suum) of cats on tracheal smooth muscle (TSM) and bronchial smooth muscle (BSM) muscarinic reactivity in vitro.

Animals

Healthy domestic shorthair cats of either sex.

Procedure

Cats were sensitized and were longterm antigen (or sham) challenge exposed for 6 weeks by aerosolization with soluble Ascaris suum. Tracheal and BSM preparations were obtained and stimulated in vitro by electrical field stimulation (EFS), acetylcholine (ACh, a muscarinic agonist), and physostigmine (an AChase inhibitor). Responses were compared with responses of comparable tissues from sham antigen challenge-exposed cats.

Results

Tracheal and BSM from sensitized, compared with sham-sensitized (control), cats had greater isometric contraction (expressed as percentage of the response observed for isotonic, 63 mM KCl-elicited contraction [% KCI]) in response to endogenous (EFS) and exogenous muscarinic receptor activation (ACh). Contractions in response to EFS by TSM from control cats were 74 % KCI vs 97 %KCI for antigen-sensitized TSM (P < 0.04). Muscarinic responses were augmented comparably by in vivo sensitization; TSM from control cats contracted to 190 % KCI vs 230 % KCl (P < 0.03) for TSM from immune-sensitized cats. Physostigmine augmented responses of all tissues to ACh so that TSM from control (290 %KCI) and antigen-sensitized (257 %KCI) cats were similar. Responses of BSM from antigen-sensitized cats had similar augmentation of contractile response to EFS and ACh.

Conclusions

Long-term in vivo antigen sensitization increases numbers of muscarinic receptors on airway smooth muscle or decreases the availability or activity of AChase in cats.

Clinical Relevance

Modulation of muscarinic receptors may be useful for treatment of asthmatic cats with in vivo airway hyperreactivity. (Am J Vet Res 1997;58:672–676)

Free access
in American Journal of Veterinary Research

SUMMARY

We assessed the effect of serotonergic inhibition by cyproheptadine on the responsiveness of tracheal smooth muscle (tsm) strips and epithelium-intact third-generation bronchial rings from immune-sensitized (Ascaris suum) cats after exposure to antigen. Cats were sensitized by im administration of antigen and adjuvant twice over a 4-week period. Sensitization was confirmed in vivo by skin testing with antigen and by physiologic airway responses after exposure to nebulized antigen. Tissues were tethered isometrically to force transducers and were actively equilibrated by exposures to KCl-substituted perfusate. Maximal response after exposure to antigen (expressed as percentage of maximal contraction of each tissue to 63 mM KCl (%KCl) was 169 ± 18% KCl for sensitized tsm and 43 ± 18% KCl for sensitized tsm pretreated with cyproheptadine (P < 0.001). Similarly, maximal response to antigen was 81 ± 27% KCl for sensitized bronchial rings, compared with 16 ± 14% KCl for sensitized bronchial rings pretreated with cyproheptadine (P = 0.05 vs control). Blockade of leukotriene synthesis by 10−6 to 10−4 M A-64077, a selective 5-lipoxygenase inhibitor, had no significant effect on peak response for either tsm (193 ± 13% KCl vs 169 ± 18% KCl for sensitized untreated tsm) or bronchial rings (79 ± 20% KCl vs 81 ± 27% KCl for sensitized untreated bronchial rings). Release of serotonin from airway tissues was confirmed by the presence of serotonin in the perfusate of 8 sensitized tsm preparations after, but not before, antigen challenge. Our data indicate that airways from immune-sensitized cats have typical immediate-type hypersensitivity responses when exposed to antigen and that these responses are inhibited by serotonin-receptor blockade, but not by blockade of 5-lipoxygenase. These data implicate serotonin as an important mediator in the immediate-type hypersensitivity reaction in the immune-sensitized airways of cats and suggest a potential role for serotonin antagonists in the clinical treatment of asthma in this species.

Free access
in American Journal of Veterinary Research