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.
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.
Kreye
V A
VA
II. Physiologisches Institut, Universität Heidelberg, Federal Republic of Germany.
Pfründer
D
D
Theiss
U
U
D000818:Animals; D001011:Aorta; D001578:Benzopyrans / Q000494:pharmacology; D001643:Bridged Bicyclo Compounds / Q000494:pharmacology*; D019086:Bridged Bicyclo Compounds, Heterocyclic; D002316:Cardiotonic Agents / Q000494:pharmacology*; D019806:Cromakalim; D003521:Cyclopropanes / Q000494:pharmacology*; D066298:In Vitro Techniques; D009119:Muscle Contraction / Q000187:drug effects; D009126:Muscle Relaxation / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects* / Q000378:metabolism / Q000502:physiology; D009638:Norepinephrine / Q000494:pharmacology; D011188:Potassium / Q000494:pharmacology; D015221:Potassium Channels / Q000187:drug effects* / Q000378:metabolism; D011758:Pyrroles / Q000494:pharmacology; D011817:Rabbits; D012413:Rubidium / Q000378:metabolism*
D001578:Benzopyrans; D001643:Bridged Bicyclo Compounds; D019086:Bridged Bicyclo Compounds, Heterocyclic; D002316:Cardiotonic Agents; D003521:Cyclopropanes; D015221:Potassium Channels; D011758:Pyrroles; D019806:Cromakalim; C059921:tedisamil; D012413:Rubidium; D011188:Potassium; D009638:Norepinephrine