EFFECT OF PILOCARPINE ON PROPRANOLOL-INDUCED BRONCHOCONSTRICTION IN ASTHMA

To investigate whether increased release of acetylcholine may be invol ved in propranolol-induced bronchoconstriction (PIB), the inhibitory e ffect of pilocarpine (Pile), an agonist of M(2)-muscarinic receptors t hat inhibits acetylcholine release from cholinergic nerves, on PIB was tested in 11 stable asthmatic subjects. The bronchial responsiveness to Pile was also measured in terms of Dmin, defined as the cumulative dose at the point where respiratory resistance (Rrs) began to increase . In PIB, the maximum increase in Rrs (Rrs max) after stopping inhalat ion for 1 min was measured. Atropine reversed PIB. After pilocarpine p retreatment at a dose equal to Dmin, Rrs max divided by baseline Rrs d ecreased significantly from 206.6 +/- 61.1 to 163.0 +/- 42.6% (mean +/ - SD) (p = 0.001). The ratio of PIB (Rrs max/baseline Rrs) with Pile t o PIB without Pile correlated inversely according to the pretreatment dose (Dmin) of Pile (p < 0.05). These results suggest increased releas e of acetylcholine in PIB and that M(2)-muscarinic receptors are at le ast in part functioning in stable asthmatic airways.