Bradykinin, lemakalim and sodium nitroprusside relax the mouse trachea in vitro by different mechanisms.

The role of K+ channels in the relaxations induced by bradykinin, lemakalim, an activator of ATP-sensitive K+ channels and sodium nitroprusside (SNP), a nitric oxide (NO) donor was examined in the isolated mouse trachea precontracted by methacholine (1 microM). 4-aminopyridine (4-AP, 0.1-2 mM), an inhibitor of 4-AP sensitive delayed rectifier channels, did not alter relaxations induced by bradykinin, lemakalim or SNP. Glibenclamide and glipizide (10-33 microM), inhibitors of ATP-sensitive K+ channels, inhibited relaxation to lemakalim without affecting responses to bradykinin and SNP. Charybdotoxin (10-100 nM) and iberiotoxin (10-100 nM), inhibitors of large conductance Ca2+-activated K+ channels, failed to inhibit relaxation to bradykinin, lemakalim or SNP. Apamin (0.1-1 microM), an inhibitor of small conductance Ca2+-activated K+ channels, did not alter responses to bradykinin, lemakalim and SNP. The results implicate that the mechanism of relaxation induced by bradykinin and SNP is different from that of lemakalim. Relaxation of the isolated mouse trachea by lemakalim appears to be mediated by ATP-sensitive K+ channels. Bradykinin and SNP induced relaxations are not mediated via Ca2+-activated K+ channels.