EFFECTS OF POTASSIUM-CHANNEL OPENER HOE-234 IN GUINEA-PIG AIRWAYS

The mechanism of the bronchospasmolytic effect of HOE 234 4-(2-oxo-1-p yrrolidinyl)-6-phenylsulphonylchromane hemihydrate), a novel opener of ATP-sensitive potassium channels, has been studied by in-vitro testin g in ring preparations of trachea and different parts of the principle bronchus of guinea-pigs, using methacholine, histamine and KCl as pre constrictors. The contribution of prostanoids was estimated in the pre sence and absence of indomethacin. Regional differences in the broncho dilatory effect of HOE 234 were compared with that of salbutamol. HOE 234 had a concentration-dependent relaxing effect on the smooth muscle preparations. Tn the absence of indomethacin no regional differences were seen for the effect of HOE 234 against the metacholine or KCl pre constriction, whereas with histamine a particularly strong relaxation was detectable in trachea. In the presence of indomethacin, distal bro nchus after methacholine and trachea after KCl preconstriction were re laxed significantly more strongly than the other parts. The relaxation of the histamine-constricted trachea rings was not increased in compa rison with that without indomethacin pretreatment. Thus the bronchospa smolytic effect of HOE 234 varied depending on the pretreatment, metho d of preconstriction and part of the ah-ways examined. It was stronges t in trachea rings with histamine preconstriction but its potency was clearly less than that of salbutamol. The latter had regionally differ ent effects, being stronger in trachea than in the bronchi for all met hods of preconstriction. The results suggest that the formation of bro nchoconstricting prostanoids can attenuate parts of the relaxing effec t of HOE 234. The possible advantages of HOE 234 as an anti-asthma dru g might be related to an effect on bronchial hyper-reactivity and mucu s secretion, because as a direct bronchodilator it is inferior to salb utamol.