Effects of selective α2‐adrenergic receptor agonists on electrical field‐stimulated contractions of isolated bronchi in horses

We investigated the effects of different selective α2‐adrenergic receptor (AR) agonists (detomidine, medetomidine, xylazine, and brimonidine) on the contractions of horse‐isolated bronchi induced by electrical field stimulation (EFS) and by carbachol. No effects were observed on the contraction induced by carbachol, while α2‐AR agonists reduced EFS‐evoked contractions in a concentration‐related fashion. The rank order of potency (pD2) was brimonidine (7.40 ± 0.20) >medetomidine (7.09 ± 0.24) >detomidine (6.13 ± 0.55) >xylazine (4.59 ± 0.16). The maximal effects (Emax) were −56.3% ± 6.3%, −40.4% ± 6.9%, −48.6% ± 9.9%, and −72.7% ± 12.7% for brimonidine, medetomidine, detomidine, and xylazine, respectively. Adrenergic block by guanethidine enhanced the potency (8.10 ± 0.05, 7.30 ± 0.15, 6.83 ± 0.41, and 5.40 ± 0.22) and the efficacy (−95.2% ± 0.7%, −45.2% ± 11.7%, −58.5% ± 9.8%, and −97.9% ± 0.6%) of brimonidine, medetomidine, detomidine, and xylazine, respectively. Selective α2‐AR antagonist, atipamezole, competitively antagonized the inhibition of EFS‐evoked contractions induced by all agonists except xylazine. These results suggest the existence of presynaptic α2‐ARs on cholinergic neurons, negatively regulating the release of acetylcholine in horse bronchial muscle, and that α2‐AR agonists may be beneficial against vagally mediated bronchoconstriction.