Modulation of ACh release from airway cholinergic nerves in horses with recurrent airway obstruction

To evaluate the functional status of neuronal alpha(2)-adrenoceptors (ARs) and beta(2)-ARs on ACh release in horses with recurrent airway obstruction (RAO), we examined the effects of the physiological agonists epinephrine (E pi) and norepinephrine (NE) and the beta(2)-agonists RR- and RR/SS-formoter ol on ACh release from airway cholinergic nerves of horses with RAO. Becaus e SS-formoterol, a distomer of the beta(2)-agonist, increases ACh release f rom airways of control horses only after the autoinhibitory muscarinic rece ptors are blocked by atropine, we also tested the hypothesis that if there is an M-2-receptor dysfunction in equine RAO, SS-formoterol should increase ACh release even in the absence of atropine. ACh release was evoked by ele ctrical field stimulation and measured by HPLC. Epi and NE caused less inhi bition of ACh release in horses with RAO than in control horses. At the cat echolamine concentration achieved during exercise (10(-7) M), the inhibitio n induced by Epi and NE was 10.8 +/- 13.2 and 3.4 +/- 6.8%, respectively, i n equine RAO versus 41.0 +/- 6.4 and 27.1 +/- 5.6%, respectively, in contro l horses. RR- and RR/SS-formoterol (10(-8) to 10(-5) M) increased ACh relea se to a similar magnitude as that in control horses. These results indicate that neuronal beta(2)-ARs are functioning; however, the alpha(2)-ARs are d ysfunctional in the airways of horses with RAO in response to circulating c atecholamines. SS-formoterol (10-8 to 10-5 M) facilitated ACh release in ho rses with RAO even in the absence of atropine. Addition of atropine did not cause significantly more augmentation of ACh release over the effect of SS -formoterol alone. The magnitude of augmentation in horses with RAO in the absence of atropine was similar to that in control horses in the presence o f atropine. The latter observations could be explained by neuronal muscarin ic-autoreceptor dysfunction in equine RAO.