1 Effects of (-)-cromakalim (lemakalim) on tension and Ca2+ mobilization induced by noradrenaline (NA) were investigated by measuring intracellular Ca2" concentration ([Ca2"]), isometric tension and production of inositol-1,4,5-trisphosphate (IP3) in smooth muscle strips of the rabbit mesenteric artery.2 In thin smooth muscle strips, 1OpUM NA produced a large phasic, followed by a small tonic increase in [Ca2'ji, which correlated well with the evoked phasic and tonic contractions, respectively. Lemakalim (0. 4 In fl-escin-skinned strips, 1OMm NA increased [Ca2+]i in Ca2+-free solution containing 50pM EGTA, 3 pM guanosine triphosphate (GTP) and 2,pM Fura 2 after the storage sites were loaded by application of 0.3/iM Ca2+ for 2 min, suggesting that Ca2+ is released from intracellular storage sites following activation of the a-adrenoceptor. Lemakalim (1 pM) did not inhibit the Ca2+ release from storage sites induced by NA. 5 We conclude that lemakalim inhibits NA-induced Ca2 + release due to inhibition of NA-induced 'P3 production in a manner dependent on the membrane potential and causes inhibition of the phasic contraction induced by NA.