Search Results

You are looking at 1 - 2 of 2 items for :

  • "airway smooth muscle" x
  • Pharmacology x
  • Refine by Access: All Content x
Clear All

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

SUMMARY

During acute bouts of recurrent airway obstruction (heaves) in horses, neutrophils that are capable of increased production of reactive oxygen species accumulate in the airways. In the study reported here, the effect of hydrogen peroxide (H2O2; 1 µM to 0.1M), one of these reactive oxygen species products, on the responses of isolated trachealis muscle of horses was determined. Before and after incubation with H2O2, contractile responses to acetylcholine, electrical field stimulation (efs), 127 mM KCl, and relaxation responses to isoproterenol and activation of the nonadrenergic noncholinergic inhibitory response (iNANC) were evaluated. Beginning at 1 mM, H2O2 contracted trachealis muscle in a concentration-dependent manner. This contraction was unaffected by atropine (1 µM), tetrodotoxin (1 µM), or 1 µM meclofenamate. Contraction of trachealis muscle in response to H2O2 is, therefore, not attributable to release of prostaglandins, acetylcholine, or other neurotransmitters. Above a concentration of 0.1 mM, H2O2 depressed the responses to efs, acetylcholine, and KCl in a concentration-dependent manner. At 0.1M, H2O2 decreased the maximal responses to efs, acetylcholine, and KCl by 62.7 ± 7.2, 60.58 ± 6.12, and 37.8 ± 9.54%, respectively. In the presence of meclofenamate (1 µM), partial but significant protection against 1 to 100 mM H2O2 was observed. In tracheal strips contracted with 0.3 µM methacholine, H2O2 had no effect on the isoproterenol concentration-response curve. Up to a concentration of 100 mM, H2O2 had no effect on iNANC response. However, in the presence of 100 mM H2O2, this response was abolished in 2 of 4 horses. We conclude that high concentrations of H2O2 affected the responses of airway smooth muscle by actions on neurotransmission, muscarinic receptors, and downstream from receptors; some of the H2O2 effects were in part mediated by cyclooxygenase products; and H2O2 had no effect on β-adrenergic or iNANC-induced relaxation.

Free access
in American Journal of Veterinary Research