Effects of selective α 2 -adrenergic receptor agonists on electrical field-stimulated contractions of isolated bronchi in horses

We investigated the effects of different selective α -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 α -AR agonists reduced EFS-evoked contractions in a concentration-related fashion. The rank order of potency (pD ) was brimonidine (7.40 ± 0.20) >medetomidine (7.09 ± 0.24) >detomidine (6.13 ± 0.55) >xylazine (4.59 ± 0.16). The maximal effects (E ) 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 α -AR antagonist, atipamezole, competitively antagonized the inhibition of EFS-evoked contractions induced by all agonists except xylazine. These results suggest the existence of presynaptic α -ARs on cholinergic neurons, negatively regulating the release of acetylcholine in horse bronchial muscle, and that α -AR agonists may be beneficial against vagally mediated bronchoconstriction.