Regulation of adrenergic nerve-mediated contraction of canine pulmonary artery by K+ channels

Abstract

The aim of the present study was to investigate the role of certain subtypes of K+ channels in nerve-evoked contractions of pulmonary artery in vitro. The lobar or segmental pulmonary arteries were dissected from dogs, cut into ring segments, and the contractile responses to electrical field stimulation (EFS) and noradrenaline were measured under isometric conditions. Addition of iberiotoxin, a big conductance Ca2+-activated K+ channel blocker, and apamin, a small conductance Ca2+-activated K+ channel blocker, did not change the resting tension but augmented the contractile responses to EFS, so that the electric stimulus frequency required to produce a half-maximal contraction (ES50) was decreased from 18.2+/-3.5 to 7.4+/-2.3 Hz (p<0.01) and from 16.8+/-2.2 to 11.4+/-2.0 Hz (p<0.05), respectively, whereas glibenclamide, an adenosine triphosphate (ATP)-sensitive K+ channel blocker, had no effect. In contrast, none of the K+ channel blockers altered the contractile response to noradrenaline. Incubation of tissues with iberiotoxin and apamin increased the release of 3H-noradrenaline evoked by EFS. We conclude that big conductance Ca2+-activated K+ channels and small conductance Ca2+-activated K+ channels may play a role in the regulation of adrenergic neurotransmission in the pulmonary artery, probably by inhibiting the exocytotic release of noradrenaline from the adrenergic nerve terminals.