Levcromakalim decreases vascular tone, cytoplasmic Ca2+ and Ca2+ sensitivity in canine basilar artery

The involvement of large conductance Ca(2+)-activated K+ channels (BK) and ATP-sensitive K+ (KATP) channels in the regulation of canine basilar arterial tone was estimated in the presence of the agonist and blockers of these channels, by simultaneously measuring the changes in intracellular Ca2+ concentration ([Ca2+]i) with the fura-2 microfluorimetric method. In the resting condition, levcromakalim reduced [Ca2+]i and vascular tone. Levcromakalim suppressed the serotonin-induced increases in [Ca2+]i and force of contraction, the maximum effects of which were much greater than those of nicardipine. The inhibitory effects of levcromakalim were blocked by glibenclamide but not by tetraethylammonium (TEA) or iberiotoxin (IbTX). In the presence of levcromakalim, the curve relating [Ca2+]i with force in the presence of serotonin at different extracellular Ca2+ concentration ([Ca2+]o) was shifted down- and right-ward compared with that in the absence of levcromakalim, suggesting that levcromakalim may reduce the Ca(2+)-sensitivity of the contractile proteins. Thus, levcromakalim may be a good candidate to suppress delayed cerebral vasospasm after subarachnoid hemorrhage.