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

Abstract

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.