The inhibitory effects of Ro 31-6930 and BRL 38227 on cholinergically-mediated bronchoconstriction in the guinea-pig

This study compares the effects of two K(+0-channel openers, Ro 31-6930 and BRL 38227, on cholinergically-evoked contraction of guinea-pig airways to examine whether either compound acts through prejunctional inhibition of the release of acetylcholine. In the isolated trachea, Ro 31-6930 and BRL 38227 evoked concentration-dependent inhibition of tone generated by electrical field stimulation with pD2 values of 7.03 (6.77-7.29) and 6.26 (5.91-6.61) respectively and of that elicited by acetylcholine with pD2 values of 7.38 (6.52-8.24) and 6.65 (6.16-7.13). Neither compound was more potent against responses to electrical field stimulation than against acetylcholine. In the anaesthetised guinea-pig, Ro 31-6930 inhibited the bronchoconstriction evoked by bilateral vagus nerve stimulation and intravenous acetylcholine with ID50 values of 12.9 +/- 3.9 and 3.6 +/- 1.3 micrograms/kg i.v. respectively. The corresponding values for BRL 38227 were 356 +/- 157 and 37.9 +/- 13.4 micrograms/kg i.v. respectively. Thus, in vivo, both compounds were more potent against acetylcholine than against vagal stimulation. These results provide indirect evidence that K(+)-channel openers do not inhibit the release of acetylcholine from parasympathetic nerves in guinea-pig airway smooth muscle.