Effects of the K+ channel blocker tedisamil on 86Rb efflux induced by cromakalim, high potassium and noradrenaline, and on mechanical tension in rabbit isolated vascular smooth muscle.

Abstract

Tedisamil, a new bradycardic agent with an inhibitory action on K+ channels in cardiac muscle, was found to inhibit in a non-competitive manner the relaxation induced by the K+ channel opener cromakalim in noradrenaline-stimulated helical strips from rabbit aortae. Tedisamil tended to be more potent in this respect than glibenclamide; the latter however competitively antagonized the cromakalim-induced relaxation. In rabbit aorta preloaded with 86Rb as a marker of K+, 10 mumol/l tedisamil inhibited the 86Rb efflux induced by 10 mumol/l cromakalim. - While the 86Rb efflux evoked by depolarization with 100 mmol/l K+ aspartate was inhibited by tedisamil, too, the rise of 86Rb efflux induced by noradrenaline was unaffected by the drug. In non-stimulated rabbit aorta, tedisamil increased mechanical tension in a concentration-dependent manner (EC50 for peak contractions: 32 mumol/l; for maintained tension: 24 mumol/l), and enhanced 86Rb efflux. Both stimulant actions were antagonized by the calcium antagonist diltiazem. In conclusion, tedisamil affects different K+ channels in vascular smooth muscle. Its stimulant effects are assumed to be secondary to membrane depolarization and subsequent activation of voltage-dependent Ca2+ channels.